Study of Two Doses of Pembrolizumab (MK-3475) Versus Docetaxel in Previously Treated Participants With Non-Small Cell Lung Cancer (MK-3475-010/KEYNOTE-010)

• ClinicalTrials.gov Identifier: NCT01905657
• Recruitment Status: Completed
• First Posted: July 23, 2013
• Results First Posted: January 18, 2017
• Last Update Posted: October 6, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non Small Cell Lung Cancer (NSCLC)
• Interventions: Biological: Pembrolizumab; Drug: Docetaxel
• Enrollment: 1034

Participant Flow

Recruitment Details	Participants who had non-small cell lung cancer (NSCLC) and whose tumors were assessed as being programmed cell death ligand 1 (PD-L1) positive were recruited for this study.
Pre-assignment Details	Per protocol, response or progression during the second and switch over pembrolizumab courses was not counted towards efficacy outcome measures, and adverse events during the second and switch over pembrolizumab courses were not counted towards safety outcome measures. Final analyses for all primary and secondary outcome measures was done at the protocol-specified cutoff of 30-Sep-2015.

Arm/Group Title	Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2
Arm/Group Description	Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
Period Title: Overall Study
Started	345	346	343
Treated	339	343	309
Received Second Course of Pembrolizumab	14	7	0
Switched Over to Pembrolizumab	0	0	8
Completed	142	159	143
Not Completed	203	187	200
Reason Not Completed
Adverse Event	23	17	18
Clinical Progression	103	78	59
Death	40	43	47
Excluded Medication	13	16	9
Lost to Follow-up	1	2	1
Physician Decision	5	8	12
Protocol Violation	2	1	1
Screen Failure	0	1	0
Withdrawal by Subject	15	21	53
Sponsor Decision	1	0	0

Baseline Characteristics

Arm/Group Title		Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2	Total
Arm/Group Description		Participants received pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.	Total of all reporting groups
Overall Number of Baseline Participants		345	346	343	1034
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	345 participants	346 participants	343 participants	1034 participants
		62.1 (9.6)	62.3 (9.7)	61.6 (9.8)	62.0 (9.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	345 participants	346 participants	343 participants	1034 participants
	Female	132 38.3%	133 38.4%	134 39.1%	399 38.6%
	Male	213 61.7%	213 61.6%	209 60.9%	635 61.4%
PD-L1 Tumor Expression Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	345 participants	346 participants	343 participants	1034 participants
	Weakly PD-L1 Positive	206 59.7%	195 56.4%	191 55.7%	592 57.3%
	Strongly PD-L1 Positive	139 40.3%	151 43.6%	152 44.3%	442 42.7%
		[1] Measure Description: PD-L1 expression was evaluated by immunohistochemistry (IHC) assay with a newly obtained tumor tissue with biopsy. If PD-L1 expression was observed in ≥1%, but ≤49% of tumor cells, a participant was categorized as weakly PD-L1 positive. If PD-L1 expression was observed in ≥50% of tumor cells, a participant was categorized as strongly PD-L1 positive.

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 September (Sep) 2015.
Time Frame	Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Per protocol, OS for the first pembrolizumab course and docetaxel treatment arms was analyzed in all randomized participants who had strongly PD-L1 positive and all PD-L1 positive OS data available and usable. Participants were included in the treatment group to which they were randomized.

Arm/Group Title		Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2
Arm/Group Description:		Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
Overall Number of Participants Analyzed		344	346	343
Median (95% Confidence Interval); Unit of Measure: Months
Strongly PD-L1 Positive	Number Analyzed	139 participants	151 participants	152 participants
		14.9 [1]; (10.4 to NA)	17.3 [1]; (11.8 to NA)	8.2; (6.4 to 10.7)
All PD-L1 Positive	Number Analyzed	344 participants	346 participants	343 participants
		10.4; (9.4 to 11.9)	12.7; (10.0 to 17.3)	8.5; (7.5 to 9.8)

[1]

Upper limit of OS not reached, due to insufficient number of deaths in the study.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 2 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with strongly PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	0.00024
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.38 to 0.77
	Estimation Comments	Numerator=Pembrolizumab 2 mg/kg Denominator=Docetaxel 75 mg/m^2

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 10 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with strongly PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	0.00002
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.36 to 0.70
	Estimation Comments	Numerator=Pembrolizumab 10 mg/kg Denominator=Docetaxel 75 mg/m^2

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 2 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	0.00076
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.58 to 0.88
	Estimation Comments	Numerator=Pembrolizumab 2 mg/kg Denominator=Docetaxel 75 mg/m^2

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 10 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	<0.00001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.61
	Confidence Interval	(2-Sided) 95%; 0.49 to 0.75
	Estimation Comments	Numerator=Pembrolizumab 10 mg/kg Denominator=Docetaxel 75 mg/m^2

2. Primary Outcome

Title	Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central radiologists' review or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm in the sum of lesions, OR the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame	Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Per protocol, PFS for the first pembrolizumab course and docetaxel treatment arms was analyzed in all randomized participants who had strongly PD-L1 positive and all PD-L1 positive PFS data available and usable. Participants were included in the treatment group to which they were randomized.

Arm/Group Title		Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2
Arm/Group Description:		Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
Overall Number of Participants Analyzed		344	346	343
Median (95% Confidence Interval); Unit of Measure: Months
Strongly PD-L1 Positive	Number Analyzed	139 participants	151 participants	152 participants
		5.2; (4.0 to 6.5)	5.2; (4.1 to 8.1)	4.1; (3.6 to 4.3)
All PD-L1 Positive	Number Analyzed	344 participants	346 participants	343 participants
		3.9; (3.1 to 4.1)	4.0; (2.6 to 4.3)	4.0; (3.1 to 4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 2 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with strongly PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	0.00009
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.77
	Estimation Comments	Numerator=Pembrolizumab 2 mg/kg Denominator=Docetaxel 75 mg/m^2

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 10 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with strongly PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	0.00007
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.78
	Estimation Comments	Numerator=Pembrolizumab 10 mg/kg Denominator=Docetaxel 75 mg/m^2

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 2 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	0.06758
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.04
	Estimation Comments	Numerator=Pembrolizumab 2 mg/kg Denominator=Docetaxel 75 mg/m^2

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 10 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	Hazard Ratio based on stratified Cox regression model with treatment as a covariate and p-value based on stratified log-rank test, in accordance with the statistical analysis plan.
Statistical Test of Hypothesis	P-Value	0.00462
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.66 to 0.94
	Estimation Comments	Numerator=Pembrolizumab 10 mg/kg Denominator=Docetaxel 75 mg/m^2

3. Primary Outcome

Title	Percentage of Participants Experiencing Adverse Events (AEs)
Description	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame	Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Per protocol, participants experiencing AEs for the first pembrolizumab course and docetaxel treatment arms were analyzed in the All Participants As Treated (APAT) population. This consisted of all participants who received at least one dose of study drug. Participants were included in the treatment group based on the study treatment they received.

Arm/Group Title	Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2
Arm/Group Description:	Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
Overall Number of Participants Analyzed	339	343	309
Measure Type: Number; Unit of Measure: Percentage of Participants
	97.6	96.2	96.1

4. Primary Outcome

Title	Percentage of Participants Discontinuing Study Drug Due to AEs
Description	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame	Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Per protocol, participants discontinuing study treatment due to AEs, for the first pembrolizumab course and docetaxel treatment arms were analyzed in the APAT population. This consisted of all participants who received at least one dose of study drug. Participants were included in the treatment group based on the study treatment they received.

Arm/Group Title	Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2
Arm/Group Description:	Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
Overall Number of Participants Analyzed	339	343	309
Measure Type: Number; Unit of Measure: Percentage of Participants
	8.3	7.6	13.6

5. Secondary Outcome

Title	Overall Response Rate (ORR) by RECIST 1.1
Description	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) based on blinded independent central radiologists' review using RECIST 1.1. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame	Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Per protocol, ORR for the first pembrolizumab course and docetaxel treatment arms was analyzed in all randomized participants who had strongly PD-L1 positive and all PD-L1 positive ORR data available and usable. Participants were included in the treatment group to which they were randomized.

Arm/Group Title		Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2
Arm/Group Description:		Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
Overall Number of Participants Analyzed		344	346	343
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Strongly PD-L1 Positive	Number Analyzed	139 participants	151 participants	152 participants
		30.2; (22.7 to 38.6)	29.1; (22.0 to 37.1)	7.9; (4.1 to 13.4)
All PD-L1 Positive	Number Analyzed	344 participants	346 participants	343 participants
		18.0; (14.1 to 22.5)	18.5; (14.5 to 23.0)	9.3; (6.5 to 12.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 2 mg/kg, Pembrolizumab 10 mg/kg
	Comments	In participants with strongly PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.66608
	Comments	P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage not equal to 0, in accordance with the statistical analysis plan.
	Method	Miettinen & Nurminen method
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -12.7 to 8.2
	Estimation Comments	This is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 10 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with strongly PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.00001
	Comments	P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage greater than 0, in accordance with the statistical analysis plan.
	Method	Miettinen & Nurminen method
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	22.2
	Confidence Interval	(2-Sided) 95%; 14.0 to 30.7
	Estimation Comments	This is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 2 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.00045
	Comments	P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage greater than 0, in accordance with the statistical analysis plan.
	Method	Miettinen & Nurminen method
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	8.7
	Confidence Interval	(2-Sided) 95%; 3.6 to 13.9
	Estimation Comments	This is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab 10 mg/kg, Docetaxel 75 mg/m^2
	Comments	In participants with PD-L1 positive tumors
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.00024
	Comments	P-value indicated for testing a difference in percentage equal to 0 versus a difference in percentage greater than 0, in accordance with the statistical analysis plan.
	Method	Miettinen & Nurminen method
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	9.1
	Confidence Interval	(2-Sided) 95%; 4.1 to 14.3
	Estimation Comments	This is an adjusted risk difference estimated by stratified Miettinen & Nurminen method.

6. Secondary Outcome

Title	Duration of Response (DOR) by RECIST 1.1
Description	DOR is measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that death or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method and is reported in weeks. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015.
Time Frame	Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

Per protocol, DOR for the first pembrolizumab course and docetaxel treatment arms was analyzed in all randomized participants who demonstrated a CR/PR and had strongly PD-L1 positive and all PD-L1 positive DOR data available and usable. Participants were included in the treatment group to which they were randomized.

Arm/Group Title		Pembrolizumab 2 mg/kg	Pembrolizumab 10 mg/kg	Docetaxel 75 mg/m^2
Arm/Group Description:		Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years. Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.	Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years. Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
Overall Number of Participants Analyzed		62	64	32
Median (Full Range); Unit of Measure: Weeks
Strongly PD-L1 Positive	Number Analyzed	42 participants	44 participants	12 participants
		NA [1]; (3 to NA)	NA [1]; (9 to NA)	35 [2]; (9 to NA)
All PD-L1 Positive	Number Analyzed	62 participants	64 participants	32 participants
		NA [1]; (3 to NA)	NA [1]; (9 to NA)	27 [2]; (6 to NA)

[1]

Median DOR and DOR upper limit not reached: No progressive disease by the time of last disease assessment.

[2]

DOR upper limit not reached: No progressive disease by the time of last disease assessment.

Adverse Events

Time Frame	Safety: Up to ~35 months for pembrolizumab first course and up to additional ~27 months for pembrolizumab second and switch over courses; All-cause mortality (ACM): Up to ~83 months for pembrolizumab first, second and switch over courses
Adverse Event Reporting Description	Safety and ACM were analyzed by treatment (pembrolizumab 2 mg/kg, 10 mg/kg, docetaxel 75 mg/m^2) and course (first, second, switch over). ACM was analyzed in all randomized participants and safety in all participants who got ≥1 dose of study drug. Per protocol disease progression of cancer was not considered an AE unless related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression", "Disease progression" unrelated to study drug are excluded as AEs.
Arm/Group Title	Pembrolizumab 2 mg/kg First Course		Pembrolizumab 10 mg/kg First Course		Docetaxel 75 mg/m^2		Pembrolizumab 2 mg/kg First Course to Pembrolizumab 200 mg Second Course		Pembrolizumab 10 mg/kg First Course to Pembrolizumab 200 mg Second Course		Docetaxel 75 mg/m^2 Switched Over to Pembrolizumab 200 mg
Arm/Group Description	Participants received pembrolizumab 2 mg/kg IV over 30 minutes Q3W for up to 2 years.		Participants received pembrolizumab 10 mg/kg IV over 30 minutes Q3W for up to 2 years.		Participants received docetaxel 75 mg/m^2 IV over 1 hour Q3W for up to 2 years.		Qualified participants who received the first course of pembrolizumab 2 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.		Qualified participants who received the first course of pembrolizumab 10 mg/kg Q3W for up to 2 years, but experienced disease progression, initiated a second course of pembrolizumab at the investigator's discretion, at 200 mg IV Q3W for up to 1 year.		Qualified participants who received docetaxel 75 mg/m^2 Q3W for up to 2 years, but experienced disease progression, switched over to pembrolizumab, at the investigator's discretion, at 200 mg IV Q3W for up to 2 years.
All-Cause Mortality
	Pembrolizumab 2 mg/kg First Course		Pembrolizumab 10 mg/kg First Course		Docetaxel 75 mg/m^2		Pembrolizumab 2 mg/kg First Course to Pembrolizumab 200 mg Second Course		Pembrolizumab 10 mg/kg First Course to Pembrolizumab 200 mg Second Course		Docetaxel 75 mg/m^2 Switched Over to Pembrolizumab 200 mg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	294/345 (85.22%)		289/346 (83.53%)		303/343 (88.34%)		4/14 (28.57%)		2/7 (28.57%)		6/8 (75.00%)
Serious Adverse Events
	Pembrolizumab 2 mg/kg First Course		Pembrolizumab 10 mg/kg First Course		Docetaxel 75 mg/m^2		Pembrolizumab 2 mg/kg First Course to Pembrolizumab 200 mg Second Course		Pembrolizumab 10 mg/kg First Course to Pembrolizumab 200 mg Second Course		Docetaxel 75 mg/m^2 Switched Over to Pembrolizumab 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	124/339 (36.58%)		133/343 (38.78%)		107/309 (34.63%)		5/14 (35.71%)		2/7 (28.57%)		1/8 (12.50%)
Blood and lymphatic system disorders
Anaemia † 1	3/339 (0.88%)	3	4/343 (1.17%)	4	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Bone marrow failure † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Eosinophilia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Febrile neutropenia † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	11/309 (3.56%)	11	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Leukopenia † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Lymph node pain † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Microcytic anaemia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Neutropenia † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	5/309 (1.62%)	5	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Normocytic anaemia † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardiac disorders
Acute coronary syndrome † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Acute myocardial infarction † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Arrhythmia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Arteriosclerosis coronary artery † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Atrial fibrillation † 1	3/339 (0.88%)	4	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Atrial flutter † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Atrial thrombosis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Atrioventricular block complete † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Bradycardia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardiac arrest † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardiac failure † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardiac failure acute † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardiac tamponade † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardio-respiratory arrest † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardiomyopathy † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cardiopulmonary failure † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Coronary artery disease † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Myocardial infarction † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pericardial effusion † 1	3/339 (0.88%)	3	2/343 (0.58%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pericarditis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	1/309 (0.32%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Restrictive cardiomyopathy † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Tachycardia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Ventricular fibrillation † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Congenital, familial and genetic disorders
Pyloric stenosis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Tracheo-oesophageal fistula † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Adrenal suppression † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hyperthyroidism † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypophysitis † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypopituitarism † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypothyroidism † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Inappropriate antidiuretic hormone secretion † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	2/339 (0.59%)	3	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Abdominal pain lower † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Ascites † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Autoimmune pancreatitis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Colitis † 1	3/339 (0.88%)	3	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Colitis ischaemic † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Constipation † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Diarrhoea † 1	1/339 (0.29%)	1	2/343 (0.58%)	2	3/309 (0.97%)	3	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Dysphagia † 1	0/339 (0.00%)	0	2/343 (0.58%)	3	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Faecaloma † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Gastric haemorrhage † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Gastritis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Ileus † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Inguinal hernia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Intra-abdominal haemorrhage † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Large intestinal obstruction † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Nausea † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Oesophageal hypomotility † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Oesophageal obstruction † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Oesophageal stenosis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pancreatitis † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Vomiting † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
General disorders
Asthenia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Axillary pain † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Chest pain † 1	2/339 (0.59%)	2	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Death † 1	3/339 (0.88%)	3	3/343 (0.87%)	3	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Fatigue † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
General physical health deterioration † 1	3/339 (0.88%)	3	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Malaise † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Mucosal inflammation † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Multiple organ dysfunction syndrome † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Oedema † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Oedema peripheral † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pain † 1	2/339 (0.59%)	2	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pyrexia † 1	3/339 (0.88%)	3	4/343 (1.17%)	4	4/309 (1.29%)	4	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hepatobiliary disorders
Autoimmune hepatitis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cholelithiasis † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hepatocellular injury † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Jaundice cholestatic † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Biliary colic † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Immune system disorders
Anaphylactic reaction † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Drug hypersensitivity † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Infections and infestations
Bronchitis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	3/309 (0.97%)	3	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cellulitis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Clostridium difficile infection † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Device related sepsis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Diverticulitis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Endocarditis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
External ear cellulitis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Gastroenteritis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Gastrointestinal infection † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Herpes zoster † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Infectious pleural effusion † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Influenza † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Large intestine infection † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Laryngitis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Lower respiratory tract infection † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Mucosal infection † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Nasopharyngitis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Osteomyelitis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Phlebitis infective † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pleural infection † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumocystis jirovecii pneumonia † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumonia † 1	20/339 (5.90%)	22	21/343 (6.12%)	22	19/309 (6.15%)	22	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumonia bacterial † 1	1/339 (0.29%)	1	2/343 (0.58%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumonia haemophilus † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumonia pneumococcal † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pyelonephritis acute † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pyopneumothorax † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Respiratory tract infection † 1	4/339 (1.18%)	4	3/343 (0.87%)	3	3/309 (0.97%)	3	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Respiratory tract infection viral † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Sepsis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Septic shock † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Staphylococcal infection † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Upper respiratory tract infection † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	3/309 (0.97%)	3	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Urinary tract infection † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Urosepsis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Vascular device infection † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Wound sepsis † 1	0/339 (0.00%)	0	1/343 (0.29%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Infective spondylitis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Otitis externa † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Injury, poisoning and procedural complications
Contusion † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Fall † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Femur fracture † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Fracture † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hip fracture † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Humerus fracture † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Incisional hernia, obstructive † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Infusion related reaction † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Injury † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Lumbar vertebral fracture † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Radiation pneumonitis † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Seroma † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Spinal compression fracture † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Thoracic vertebral fracture † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Traumatic intracranial haemorrhage † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Upper limb fracture † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Aspartate aminotransferase increased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Blood alkaline phosphatase increased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Blood bilirubin increased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Blood creatine phosphokinase increased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Blood creatinine increased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
C-reactive protein increased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Neutrophil count decreased † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Platelet count decreased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	3/309 (0.97%)	3	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Dehydration † 1	1/339 (0.29%)	1	2/343 (0.58%)	2	4/309 (1.29%)	4	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Diabetes mellitus † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Diabetic ketoacidosis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypercalcaemia † 1	1/339 (0.29%)	1	5/343 (1.46%)	7	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypertriglyceridaemia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypoalbuminaemia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypoglycaemia † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypokalaemia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hyponatraemia † 1	1/339 (0.29%)	1	2/343 (0.58%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypophosphataemia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Type 1 diabetes mellitus † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Arthritis † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Back pain † 1	3/339 (0.88%)	3	2/343 (0.58%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Bone pain † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Bursitis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Muscle fatigue † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Muscle haemorrhage † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Muscle necrosis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Musculoskeletal chest pain † 1	1/339 (0.29%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Musculoskeletal pain † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Myopathy † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Neck pain † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Osteoporosis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Osteoporotic fracture † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pain in extremity † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Spinal osteoarthritis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Spinal stenosis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Synovitis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Tendonitis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Tenosynovitis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Bronchial carcinoma † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cancer pain † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Gastric cancer † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Lung neoplasm malignant † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Malignant pleural effusion † 1	1/339 (0.29%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Metastases to central nervous system † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Paraneoplastic syndrome † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Tumour associated fever † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Tumour pain † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Nervous system disorders
Brain oedema † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cerebral ischaemia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cerebrovascular accident † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Cognitive disorder † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Dizziness † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Haemorrhage intracranial † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hemiparesis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Ischaemic stroke † 1	1/339 (0.29%)	1	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Myelitis transverse † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Neurological decompensation † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Peripheral sensory neuropathy † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Spinal cord compression † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Syncope † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Toxic leukoencephalopathy † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Transient ischaemic attack † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Nervous system disorder † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Product Issues
Device dislocation † 1	0/339 (0.00%)	0	1/343 (0.29%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Psychiatric disorders
Anxiety † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Completed suicide † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Confusional state † 1	3/339 (0.88%)	4	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Delirium † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Disorientation † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Mental status changes † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Suicide attempt † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	2/339 (0.59%)	2	2/343 (0.58%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Bladder hypertrophy † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Haematuria † 1	1/339 (0.29%)	2	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Renal failure † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Tubulointerstitial nephritis † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Urinary bladder polyp † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Urinary retention † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Reproductive system and breast disorders
Erectile dysfunction † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Bronchial haemorrhage † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Chronic obstructive pulmonary disease † 1	6/339 (1.77%)	6	1/343 (0.29%)	3	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Dyspnoea † 1	6/339 (1.77%)	6	2/343 (0.58%)	2	6/309 (1.94%)	7	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Haemoptysis † 1	3/339 (0.88%)	3	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypoxia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Interstitial lung disease † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Painful respiration † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pleural effusion † 1	3/339 (0.88%)	3	4/343 (1.17%)	5	3/309 (0.97%)	3	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pleuritic pain † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumonia aspiration † 1	1/339 (0.29%)	1	2/343 (0.58%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumonitis † 1	14/339 (4.13%)	15	10/343 (2.92%)	10	2/309 (0.65%)	2	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Pneumothorax † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	3/309 (0.97%)	3	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pulmonary embolism † 1	8/339 (2.36%)	8	8/343 (2.33%)	8	5/309 (1.62%)	5	2/14 (14.29%)	2	0/7 (0.00%)	0	0/8 (0.00%)	0
Pulmonary haemorrhage † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pulmonary hypertension † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pulmonary oedema † 1	1/339 (0.29%)	1	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Pulmonary vascular disorder † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Respiratory distress † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Respiratory failure † 1	2/339 (0.59%)	2	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Skin and subcutaneous tissue disorders
Drug eruption † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Rash maculo-papular † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Embolism † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypertension † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypotension † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Peripheral artery occlusion † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Peripheral ischaemia † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Superior vena cava occlusion † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Superior vena cava syndrome † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pembrolizumab 2 mg/kg First Course		Pembrolizumab 10 mg/kg First Course		Docetaxel 75 mg/m^2		Pembrolizumab 2 mg/kg First Course to Pembrolizumab 200 mg Second Course		Pembrolizumab 10 mg/kg First Course to Pembrolizumab 200 mg Second Course		Docetaxel 75 mg/m^2 Switched Over to Pembrolizumab 200 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	312/339 (92.04%)		301/343 (87.76%)		279/309 (90.29%)		9/14 (64.29%)		5/7 (71.43%)		7/8 (87.50%)
Blood and lymphatic system disorders
Anaemia † 1	37/339 (10.91%)	50	32/343 (9.33%)	43	61/309 (19.74%)	71	2/14 (14.29%)	3	0/7 (0.00%)	0	1/8 (12.50%)	2
Neutropenia † 1	1/339 (0.29%)	1	2/343 (0.58%)	3	47/309 (15.21%)	103	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Iron deficiency anaemia † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/6 (16.67%)	1
Thrombocytopenia † 1	4/339 (1.18%)	4	6/343 (1.75%)	6	7/309 (2.27%)	7	0/14 (0.00%)	0	1/7 (14.29%)	1	0/6 (0.00%)	0
Endocrine disorders
Hyperthyroidism † 1	12/339 (3.54%)	13	19/343 (5.54%)	19	3/309 (0.97%)	3	2/14 (14.29%)	2	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypothyroidism † 1	29/339 (8.55%)	30	29/343 (8.45%)	34	1/309 (0.32%)	1	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Eye disorders
Lacrimation increased † 1	2/339 (0.59%)	2	2/343 (0.58%)	3	17/309 (5.50%)	18	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Conjunctival haemorrhage † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Gastrointestinal disorders
Abdominal pain † 1	20/339 (5.90%)	24	21/343 (6.12%)	23	13/309 (4.21%)	17	2/14 (14.29%)	2	0/7 (0.00%)	0	1/8 (12.50%)	1
Constipation † 1	59/339 (17.40%)	65	57/343 (16.62%)	64	41/309 (13.27%)	47	1/14 (7.14%)	2	1/7 (14.29%)	1	1/8 (12.50%)	1
Diarrhoea † 1	62/339 (18.29%)	91	51/343 (14.87%)	62	81/309 (26.21%)	111	1/14 (7.14%)	2	1/7 (14.29%)	1	2/8 (25.00%)	5
Nausea † 1	87/339 (25.66%)	105	75/343 (21.87%)	92	65/309 (21.04%)	80	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Stomatitis † 1	19/339 (5.60%)	22	13/343 (3.79%)	15	49/309 (15.86%)	72	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Vomiting † 1	51/339 (15.04%)	60	48/343 (13.99%)	59	32/309 (10.36%)	37	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Abdominal pain upper † 1	11/339 (3.24%)	11	12/343 (3.50%)	13	7/309 (2.27%)	7	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Dyspepsia † 1	10/339 (2.95%)	13	5/343 (1.46%)	6	14/309 (4.53%)	14	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Oral pain † 1	2/339 (0.59%)	3	0/343 (0.00%)	0	6/309 (1.94%)	6	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Salivary hypersecretion † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
General disorders
Asthenia † 1	44/339 (12.98%)	60	45/343 (13.12%)	59	51/309 (16.50%)	72	0/14 (0.00%)	0	2/7 (28.57%)	2	0/8 (0.00%)	0
Chest pain † 1	25/339 (7.37%)	26	32/343 (9.33%)	40	22/309 (7.12%)	23	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Fatigue † 1	102/339 (30.09%)	122	88/343 (25.66%)	107	106/309 (34.30%)	131	0/14 (0.00%)	0	1/7 (14.29%)	1	1/8 (12.50%)	1
Oedema peripheral † 1	30/339 (8.85%)	35	28/343 (8.16%)	30	34/309 (11.00%)	37	1/14 (7.14%)	1	1/7 (14.29%)	1	1/8 (12.50%)	1
Pyrexia † 1	51/339 (15.04%)	68	40/343 (11.66%)	64	42/309 (13.59%)	56	2/14 (14.29%)	2	0/7 (0.00%)	0	0/8 (0.00%)	0
Gait disturbance † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	4/309 (1.29%)	4	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Influenza like illness † 1	9/339 (2.65%)	15	12/343 (3.50%)	16	3/309 (0.97%)	6	1/14 (7.14%)	1	0/7 (0.00%)	0	1/8 (12.50%)	1
Infusion site extravasation † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	4/309 (1.29%)	4	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Injection site haemorrhage † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Oedema † 1	7/339 (2.06%)	9	3/343 (0.87%)	3	6/309 (1.94%)	6	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Infections and infestations
Nasopharyngitis † 1	20/339 (5.90%)	26	23/343 (6.71%)	29	16/309 (5.18%)	16	0/14 (0.00%)	0	1/7 (14.29%)	1	1/8 (12.50%)	1
Upper respiratory tract infection † 1	18/339 (5.31%)	19	18/343 (5.25%)	26	11/309 (3.56%)	12	1/14 (7.14%)	2	2/7 (28.57%)	3	0/8 (0.00%)	0
Urinary tract infection † 1	19/339 (5.60%)	21	10/343 (2.92%)	12	9/309 (2.91%)	10	0/14 (0.00%)	0	1/7 (14.29%)	1	1/8 (12.50%)	5
Cystitis † 1	5/339 (1.47%)	5	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Fungal infection † 1	3/339 (0.88%)	5	2/343 (0.58%)	2	2/309 (0.65%)	2	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Influenza † 1	8/339 (2.36%)	8	3/343 (0.87%)	3	3/309 (0.97%)	3	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Liver abscess † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Paraspinal abscess † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Respiratory tract infection † 1	14/339 (4.13%)	16	7/343 (2.04%)	12	9/309 (2.91%)	10	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Injury, poisoning and procedural complications
Contusion † 1	4/339 (1.18%)	4	5/343 (1.46%)	6	2/309 (0.65%)	3	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Fall † 1	4/339 (1.18%)	5	3/343 (0.87%)	3	3/309 (0.97%)	3	0/14 (0.00%)	0	1/7 (14.29%)	1	1/8 (12.50%)	1
Joint dislocation † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Skin laceration † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Tendon injury † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	26/339 (7.67%)	35	20/343 (5.83%)	22	5/309 (1.62%)	6	1/14 (7.14%)	2	1/7 (14.29%)	1	0/8 (0.00%)	0
Aspartate aminotransferase increased † 1	20/339 (5.90%)	29	21/343 (6.12%)	24	4/309 (1.29%)	4	1/14 (7.14%)	2	1/7 (14.29%)	1	0/8 (0.00%)	0
Blood alkaline phosphatase increased † 1	12/339 (3.54%)	16	19/343 (5.54%)	19	5/309 (1.62%)	5	1/14 (7.14%)	2	0/7 (0.00%)	0	0/8 (0.00%)	0
Blood creatinine increased † 1	19/339 (5.60%)	26	17/343 (4.96%)	20	4/309 (1.29%)	4	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Neutrophil count decreased † 1	3/339 (0.88%)	4	3/343 (0.87%)	4	25/309 (8.09%)	45	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Weight decreased † 1	32/339 (9.44%)	37	33/343 (9.62%)	34	11/309 (3.56%)	13	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
White blood cell count decreased † 1	0/339 (0.00%)	0	3/343 (0.87%)	6	17/309 (5.50%)	29	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Amylase increased † 1	0/339 (0.00%)	0	1/343 (0.29%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Blood thyroid stimulating hormone increased † 1	5/339 (1.47%)	5	4/343 (1.17%)	6	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Gamma-glutamyltransferase increased † 1	15/339 (4.42%)	20	5/343 (1.46%)	5	3/309 (0.97%)	4	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Serum ferritin decreased † 1	1/339 (0.29%)	1	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	104/339 (30.68%)	123	80/343 (23.32%)	93	74/309 (23.95%)	87	1/14 (7.14%)	1	2/7 (28.57%)	2	4/8 (50.00%)	4
Hyperglycaemia † 1	18/339 (5.31%)	27	15/343 (4.37%)	27	12/309 (3.88%)	13	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Folate deficiency † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Hypercholesterolaemia † 1	6/339 (1.77%)	7	7/343 (2.04%)	8	1/309 (0.32%)	1	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Hypertriglyceridaemia † 1	10/339 (2.95%)	14	10/343 (2.92%)	15	3/309 (0.97%)	4	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Hypokalaemia † 1	15/339 (4.42%)	18	8/343 (2.33%)	16	11/309 (3.56%)	12	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	48/339 (14.16%)	67	42/343 (12.24%)	50	29/309 (9.39%)	34	0/14 (0.00%)	0	2/7 (28.57%)	3	0/8 (0.00%)	0
Back pain † 1	41/339 (12.09%)	48	45/343 (13.12%)	51	23/309 (7.44%)	25	1/14 (7.14%)	2	1/7 (14.29%)	1	0/8 (0.00%)	0
Musculoskeletal pain † 1	39/339 (11.50%)	48	37/343 (10.79%)	41	10/309 (3.24%)	16	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Myalgia † 1	20/339 (5.90%)	28	15/343 (4.37%)	18	35/309 (11.33%)	52	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	2
Pain in extremity † 1	22/339 (6.49%)	23	26/343 (7.58%)	27	13/309 (4.21%)	16	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Flank pain † 1	3/339 (0.88%)	3	1/343 (0.29%)	1	2/309 (0.65%)	2	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Spondylolisthesis † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Nervous system disorders
Dizziness † 1	30/339 (8.85%)	37	24/343 (7.00%)	26	12/309 (3.88%)	15	0/14 (0.00%)	0	1/7 (14.29%)	1	1/8 (12.50%)	1
Dysgeusia † 1	5/339 (1.47%)	5	8/343 (2.33%)	8	19/309 (6.15%)	24	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Headache † 1	42/339 (12.39%)	47	35/343 (10.20%)	43	22/309 (7.12%)	25	0/14 (0.00%)	0	1/7 (14.29%)	1	1/8 (12.50%)	1
Neuropathy peripheral † 1	8/339 (2.36%)	9	9/343 (2.62%)	9	37/309 (11.97%)	39	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Paraesthesia † 1	7/339 (2.06%)	9	8/343 (2.33%)	9	20/309 (6.47%)	22	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Peripheral sensory neuropathy † 1	5/339 (1.47%)	7	6/343 (1.75%)	6	17/309 (5.50%)	17	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Balance disorder † 1	3/339 (0.88%)	3	1/343 (0.29%)	2	1/309 (0.32%)	1	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Cerebral ischaemia † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Dysarthria † 1	0/339 (0.00%)	0	1/343 (0.29%)	1	4/309 (1.29%)	4	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Facial paralysis † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	0/309 (0.00%)	0	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Sciatica † 1	4/339 (1.18%)	5	2/343 (0.58%)	2	1/309 (0.32%)	1	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Amnesia † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Psychiatric disorders
Anxiety † 1	18/339 (5.31%)	19	16/343 (4.66%)	16	9/309 (2.91%)	9	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Insomnia † 1	27/339 (7.96%)	29	22/343 (6.41%)	22	22/309 (7.12%)	24	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Depressed mood † 1	0/339 (0.00%)	0	3/343 (0.87%)	4	1/309 (0.32%)	1	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Renal and urinary disorders
Renal failure † 1	4/339 (1.18%)	4	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	82/339 (24.19%)	104	75/343 (21.87%)	94	43/309 (13.92%)	47	2/14 (14.29%)	2	0/7 (0.00%)	0	1/8 (12.50%)	1
Dyspnoea † 1	81/339 (23.89%)	92	79/343 (23.03%)	95	65/309 (21.04%)	71	2/14 (14.29%)	2	1/7 (14.29%)	1	0/8 (0.00%)	0
Haemoptysis † 1	26/339 (7.67%)	37	26/343 (7.58%)	33	20/309 (6.47%)	29	1/14 (7.14%)	1	1/7 (14.29%)	1	0/8 (0.00%)	0
Productive cough † 1	21/339 (6.19%)	30	30/343 (8.75%)	32	10/309 (3.24%)	12	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Chronic obstructive pulmonary disease † 1	3/339 (0.88%)	4	8/343 (2.33%)	8	1/309 (0.32%)	1	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Dysphonia † 1	13/339 (3.83%)	14	8/343 (2.33%)	9	9/309 (2.91%)	9	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Oropharyngeal pain † 1	9/339 (2.65%)	11	12/343 (3.50%)	12	7/309 (2.27%)	7	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Pneumonitis † 1	8/339 (2.36%)	9	7/343 (2.04%)	8	1/309 (0.32%)	1	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Pulmonary haemorrhage † 1	0/339 (0.00%)	0	0/343 (0.00%)	0	1/309 (0.32%)	1	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Sputum discoloured † 1	2/339 (0.59%)	2	1/343 (0.29%)	1	0/309 (0.00%)	0	0/14 (0.00%)	0	1/7 (14.29%)	2	0/8 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia † 1	6/339 (1.77%)	6	5/343 (1.46%)	5	110/309 (35.60%)	112	0/14 (0.00%)	0	0/7 (0.00%)	0	0/8 (0.00%)	0
Dry skin † 1	15/339 (4.42%)	19	19/343 (5.54%)	25	8/309 (2.59%)	8	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Pruritus † 1	45/339 (13.27%)	62	52/343 (15.16%)	76	11/309 (3.56%)	11	4/14 (28.57%)	4	0/7 (0.00%)	0	1/8 (12.50%)	1
Rash † 1	48/339 (14.16%)	62	59/343 (17.20%)	78	22/309 (7.12%)	22	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Erythema † 1	3/339 (0.88%)	3	7/343 (2.04%)	7	5/309 (1.62%)	5	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
Macule † 1	0/339 (0.00%)	0	2/343 (0.58%)	2	0/309 (0.00%)	0	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	1
Skin exfoliation † 1	2/339 (0.59%)	2	0/343 (0.00%)	0	2/309 (0.65%)	2	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Skin lesion † 1	4/339 (1.18%)	4	3/343 (0.87%)	3	1/309 (0.32%)	2	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Vascular disorders
Embolism † 1	2/339 (0.59%)	2	1/343 (0.29%)	1	1/309 (0.32%)	1	1/14 (7.14%)	1	0/7 (0.00%)	0	0/8 (0.00%)	0
Hypertension † 1	15/339 (4.42%)	16	12/343 (3.50%)	12	6/309 (1.94%)	7	0/14 (0.00%)	0	0/7 (0.00%)	0	1/8 (12.50%)	3
Orthostatic hypotension † 1	1/339 (0.29%)	1	1/343 (0.29%)	1	2/309 (0.65%)	3	0/14 (0.00%)	0	1/7 (14.29%)	1	0/8 (0.00%)	0
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

Publications of Results:

Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-1550. doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.

Jemielita T, Li XN, Piperdi B, Zhou W, Burke T, Chen C. Overall Survival With Second-Line Pembrolizumab in Patients With Non-Small-Cell Lung Cancer: Randomized Phase III Clinical Trial Versus Propensity-Adjusted Real-World Data. JCO Clin Cancer Inform. 2021 Jan;5:56-65. doi: 10.1200/CCI.20.00099.

Lala M, Li TR, de Alwis DP, Sinha V, Mayawala K, Yamamoto N, Siu LL, Chartash E, Aboshady H, Jain L. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation. Eur J Cancer. 2020 May;131:68-75. doi: 10.1016/j.ejca.2020.02.016. Epub 2020 Apr 15. Erratum In: Eur J Cancer. 2021 Feb;144:400.

Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, Novello S, Szalai Z, Gubens MA, Su WC, Ceresoli GL, Samkari A, Jensen EH, Lubiniecki GM, Baas P. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1-Positive, Advanced Non-Small-Cell Lung Cancer in the KEYNOTE-010 Study. J Clin Oncol. 2020 May 10;38(14):1580-1590. doi: 10.1200/JCO.19.02446. Epub 2020 Feb 20.

van Vugt MJH, Stone JA, De Greef RHJMM, Snyder ES, Lipka L, Turner DC, Chain A, Lala M, Li M, Robey SH, Kondic AG, De Alwis D, Mayawala K, Jain L, Freshwater T. Immunogenicity of pembrolizumab in patients with advanced tumors. J Immunother Cancer. 2019 Aug 8;7(1):212. doi: 10.1186/s40425-019-0663-4.

Barlesi F, Garon EB, Kim DW, Felip E, Han JY, Kim JH, Ahn MJ, Fidler MJ, Gubens MA, de Castro G Jr, Surmont V, Li Q, Deitz AC, Lubiniecki GM, Herbst RS. Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1-Expressing NSCLC. J Thorac Oncol. 2019 May;14(5):793-801. doi: 10.1016/j.jtho.2019.01.016. Epub 2019 Jan 31. Erratum In: J Thorac Oncol. 2019 Jul;14(7):1306.

Herbst RS, Baas P, Perez-Gracia JL, Felip E, Kim DW, Han JY, Molina JR, Kim JH, Dubos Arvis C, Ahn MJ, Majem M, Fidler MJ, Surmont V, de Castro G Jr, Garrido M, Shentu Y, Emancipator K, Samkari A, Jensen EH, Lubiniecki GM, Garon EB. Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. Ann Oncol. 2019 Feb 1;30(2):281-289. doi: 10.1093/annonc/mdy545.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01905657
• Other Study ID Numbers: 3475-010; 2012-004391-19 ( EudraCT Number ); 132355 ( Registry Identifier: Japic-CTI ); MK-3475-010 ( Other Identifier: Merck ); KEYNOTE-010 ( Other Identifier: Merck )
• First Submitted: July 18, 2013
• First Posted: July 23, 2013
• Results First Submitted: September 15, 2016
• Results First Posted: January 18, 2017
• Last Update Posted: October 6, 2021