Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC (SELECT-1)

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ClinicalTrials.gov Identifier: NCT01933932

Recruitment Status : Active, not recruiting

First Posted : September 2, 2013

Results First Posted : August 29, 2017

Last Update Posted : October 17, 2023

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Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV
Interventions	Drug: Selumetinib Drug: Docetaxel Drug: Placebo Drug: Pegylated G-CSF
Enrollment	510

Participant Flow

Recruitment Details	This study started with an assessment visit where a tumour KRAS mutation assessment was performed, eligibility assessments were performed and informed consent obtained. Eligible patients were randomised at the next visit. Patients then received double-blinded study treatment, were seen and assessments performed until objective disease progression.
Pre-assignment Details	Eligible patients randomised in a ratio of 1:1 to receive selumetinib (AZD6244; ARRY-142886) 75 mg bd in combination with docetaxel 75 mg/m2 or placebo in combination with docetaxel 75 mg/m2. They were stratified based on their WHO performance status and tumour histology. 510 patients enrolled and 510 randomised.


Arm/Group Title	Selumetinib + Docetaxel	Placebo + Docetaxel
Arm/Group Description	Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...
Arm/Group Description	Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Period Title: Overall Study
Started	254	256
Completed	70 ^[1]	78 ^[1]
Not Completed	184	178
Reason Not Completed
Death	173	163
Withdrawal by Subject	11	14
Eligibility criteria not fulfilled	0	1
[1] These were the number of patients who were still ongoing at data cut-off

Baseline Characteristics

Arm/Group Title		Selumetinib + Docetaxel	Placebo + Docetaxel	Total
Arm/Group Description		Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...	Total of all reporting groups
Arm/Group Description		Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.	Total of all reporting groups
Overall Number of Baseline Participants		254	256	510
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	254 participants	256 participants	510 participants
		61.9 (8.48)	60.9 (8.08)	61.4 (8.30)
Age, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	254 participants	256 participants	510 participants
>=65 years		97	83	180
<65 years		157	173	330
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	254 participants	256 participants	510 participants
	Female	96 37.8%	111 43.4%	207 40.6%
	Male	158 62.2%	145 56.6%	303 59.4%
Race Measure Type: Number Unit of measure: Participants	Number Analyzed	254 participants	256 participants	510 participants
White		241	243	484
Black or African American		5	1	6
Asian		1	4	5
American Indian or Alaska Native		3	2	5
Other		4	6	10
Ethnic group Measure Type: Number Unit of measure: Participants	Number Analyzed	254 participants	256 participants	510 participants
Hispanic or Latino		14	15	29
Not Hispanic or Latino		240	241	481

Outcome Measures

1.Primary Outcome


Title	Progression-Free Survival (PFS)
Description	Progression free survival is defined as the time from randomisation un...
Description	Progression free survival is defined as the time from randomisation until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression)
Time Frame	Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population comprised of all randomised patients.


Arm/Group Title	Selumetinib + Docetaxel	Placebo + Docetaxel
Arm/Group Description:	Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...
Arm/Group Description:	Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Overall Number of Participants Analyzed	254	256
Median (Inter-Quartile Range) Unit of Measure: Months
	3.9 (1.5 to 5.9)	2.8 (1.4 to 5.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib + Docetaxel, Placebo + Docetaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4355
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Analysis stratified by WHO performance status at randomisation.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.77 to 1.12
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Survival (OS)
Description	Overall Survival is defined as the time from the date of randomisation...
Description	Overall Survival is defined as the time from the date of randomisation until death due to any cause.
Time Frame	Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population comprised of all randomised patients.


Arm/Group Title	Selumetinib + Docetaxel	Placebo + Docetaxel
Arm/Group Description:	Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...
Arm/Group Description:	Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Overall Number of Participants Analyzed	254	256
Median (Inter-Quartile Range) Unit of Measure: Months
	8.7 (3.6 to 16.8)	7.9 (3.8 to 20.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib + Docetaxel, Placebo + Docetaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6431
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Analysis stratified by WHO performance status at randomisation.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95% 0.85 to 1.30
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Objective Response Rate (ORR)
Description	ORR is defined as the number (%) of subjects with at least one overall...
Description	ORR is defined as the number (%) of subjects with at least one overall visit response of complete response (CR) or partial response (PR). Per RECIST v1.1 for target lesions and assessed by CT/MRI: CR - disappearance of all target lesions; PR - >=30% decrease in the sum of the longest diameter of target lesion. (Non-target lesion and new lesion results are also taken into account for the overall visit result)
Time Frame	Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population comprised of all randomised patients.


Arm/Group Title	Selumetinib + Docetaxel	Placebo + Docetaxel
Arm/Group Description:	Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...
Arm/Group Description:	Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Overall Number of Participants Analyzed	254	256
Measure Type: Number Unit of Measure: Number of responders
	51	35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib + Docetaxel, Placebo + Docetaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0515
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Analysis stratified by WHO performance status at randomisation

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95% 1.00 to 2.62
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Duration of Response (DoR)
Description	Duration of response is defined as the time from the date of first doc...
Description	Duration of response is defined as the time from the date of first documented response until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression)
Time Frame	Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) population comprised of all randomised patients.


Arm/Group Title	Selumetinib + Docetaxel	Placebo + Docetaxel
Arm/Group Description:	Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...
Arm/Group Description:	Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Overall Number of Participants Analyzed	51	35
Median (95% Confidence Interval) Unit of Measure: Days
	88.0 (82.0 to 126.0)	136.0 (86.0 to 169.0)

5.Secondary Outcome


Title	Symptom Improvement Rate Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
Description	The symptom improvement rate will be defined as the number (%) of pati...
Description	The symptom improvement rate will be defined as the number (%) of patients with two consecutive assessments at least 18 days apart (ie 21 days allowing a visit window of 3 days) which showed a clinically meaningful improvement in symptoms from baseline (defined as a decrease in the ASBI from baseline ≥10). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.
Time Frame	Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) patients who have a baseline ASBI score >= 10


Arm/Group Title	Selumetinib + Docetaxel	Placebo + Docetaxel
Arm/Group Description:	Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...
Arm/Group Description:	Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Overall Number of Participants Analyzed	205	217
Measure Type: Number Unit of Measure: Number of patients with improvements
	49	46

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib + Docetaxel, Placebo + Docetaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5007
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	Analysis stratified by WHO performance status at randomisation

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95% 0.74 to 1.86
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Time to Symptom Progression Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
Description	Time to symptom progression will be defined as the time from randomiza...
Description	Time to symptom progression will be defined as the time from randomization until the date of first clinically meaningful symptom deterioration (defined as an increase in the ASBI from baseline ≥10), or death (by any cause). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index.
Time Frame	Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) patients who have a baseline ASBI score <= 90


Arm/Group Title	Selumetinib + Docetaxel	Placebo + Docetaxel
Arm/Group Description:	Three 25mg selumetinib capsules wil...	Three placebo capsules will be admi...
Arm/Group Description:	Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.
Overall Number of Participants Analyzed	234	247
Median (Inter-Quartile Range) Unit of Measure: Months
	1.6 (0.4 to 4.6)	1.3 (0.3 to 4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Selumetinib + Docetaxel, Placebo + Docetaxel
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3438
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Analysis stratified by WHO performance status at randomisation.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.74 to 1.11
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	AEs were collected from the time of signature of informed consent to the main study until 30 days (± 7 days) after the last dose of the last study treatment.
Adverse Event Reporting Description	The total number of patients at risk are taken from the number of patients in the safety analysis set. They are patients who received at least one dose of randomised investigational product (selumetinib/placebo). (The numbers in the participant flow module are randomised patients).

Arm/Group Title	Placebo + Docetaxel		Selumetinib + Docetaxel
Arm/Group Description	Three placebo capsules will be admi...		Three 25mg selumetinib capsules wil...
Arm/Group Description	Three placebo capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle.		Three 25mg selumetinib capsules will be administered orally uninterrupted twice daily in combination with docetaxel 75 mg/m2 intravenously administered on day 1 of each 21 day cycle
All-Cause Mortality
	Placebo + Docetaxel		Selumetinib + Docetaxel
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Placebo + Docetaxel		Selumetinib + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	82/254 (32.28%)		124/251 (49.40%)
Blood and lymphatic system disorders
Anaemia ^† 1	4/254 (1.57%)	4	3/251 (1.20%)	3
Febrile neutropenia ^† 1	2/254 (0.79%)	2	4/251 (1.59%)	4
Neutropenia ^† 1	1/254 (0.39%)	1	5/251 (1.99%)	5
Thrombocytopenia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Cardiac disorders
Acute myocardial infarction ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Cardiac failure ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Cardiac failure congestive ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Cardiovascular insufficiency ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Coronary artery dissection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pericardial effusion ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Pericarditis constrictive ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Sinus bradycardia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Supraventricular tachycardia ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Eye disorders
Retinal vein thrombosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Gastrointestinal disorders
Abdominal pain ^† 1	2/254 (0.79%)	2	2/251 (0.80%)	2
Abdominal pain upper ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Colitis ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Constipation ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Diarrhoea ^† 1	3/254 (1.18%)	3	10/251 (3.98%)	10
Diverticular perforation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Duodenal ulcer ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Dysphagia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Gastric ulcer perforation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Gastrooesophageal reflux disease ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Haemorrhoids ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Intestinal obstruction ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lower gastrointestinal haemorrhage ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Proctitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Rectal haemorrhage ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Retroperitoneal haemorrhage ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Stomatitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Subileus ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Upper gastrointestinal haemorrhage ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Vomiting ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
General disorders
Asthenia ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Euthanasia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Fatigue ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
General physical health deterioration ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Malaise ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Oedema peripheral ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Pyrexia ^† 1	5/254 (1.97%)	9	7/251 (2.79%)	8
Immune system disorders
Anaphylactic reaction ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Anaphylactic shock ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hypersensitivity ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infections and infestations
Anal abscess ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Arthritis infective ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Bronchitis ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Device related infection ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Diverticulitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Herpes zoster ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infected skin ulcer ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infectious pleural effusion ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infective exacerbation of chronic obstructive airways disease ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	2
Lower respiratory tract infection ^† 1	5/254 (1.97%)	5	4/251 (1.59%)	4
Lung abscess ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lung infection ^† 1	2/254 (0.79%)	2	3/251 (1.20%)	3
Neutropenic sepsis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Pneumocystis jirovecii pneumonia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Pneumonia ^† 1	11/254 (4.33%)	14	17/251 (6.77%)	20
Pneumonia viral ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Respiratory tract infection ^† 1	2/254 (0.79%)	3	6/251 (2.39%)	6
Respiratory tract infection viral ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Sepsis ^† 1	1/254 (0.39%)	1	7/251 (2.79%)	7
Staphylococcal infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Streptococcal bacteraemia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Urinary tract infection ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Urosepsis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Injury, poisoning and procedural complications
Femoral neck fracture ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hip fracture ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Post procedural complication ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Radiation oesophagitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Toxicity to various agents ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Investigations
C-reactive protein increased ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	3
Ejection fraction decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Metabolism and nutrition disorders
Cachexia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Dehydration ^† 1	3/254 (1.18%)	3	6/251 (2.39%)	6
Hyperglycaemia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hyponatraemia ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Back pain ^† 1	3/254 (1.18%)	3	0/251 (0.00%)	0
Musculoskeletal chest pain ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pathological fracture ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Metastases to meninges ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Metastases to peritoneum ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Oesophageal adenocarcinoma ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Nervous system disorders
Cerebral haemorrhage ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Cerebral ischaemia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Cerebrovascular accident ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Cognitive disorder ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Dropped head syndrome ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Neurological decompensation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	2
Polyneuropathy ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Somnolence ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Syncope ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	3
Psychiatric disorders
Confusional state ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Neurogenic bladder ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Chronic obstructive pulmonary disease ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Dyspnoea ^† 1	4/254 (1.57%)	5	7/251 (2.79%)	7
Dyspnoea exertional ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Haemoptysis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hypoxia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Interstitial lung disease ^† 1	1/254 (0.39%)	1	4/251 (1.59%)	4
Pleural effusion ^† 1	3/254 (1.18%)	5	1/251 (0.40%)	1
Pneumonitis ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
Pneumothorax ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Pulmonary embolism ^† 1	3/254 (1.18%)	3	4/251 (1.59%)	4
Respiratory failure ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Sleep apnoea syndrome ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Vascular disorders
Deep vein thrombosis ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Hypotension ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Internal haemorrhage ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Superior vena cava syndrome ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Venous thrombosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Placebo + Docetaxel		Selumetinib + Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	235/254 (92.52%)		244/251 (97.21%)
Blood and lymphatic system disorders
Anaemia ^† 1	37/254 (14.57%)	40	46/251 (18.33%)	50
Anaemia of malignant disease ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Febrile bone marrow aplasia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Leukocytosis ^† 1	4/254 (1.57%)	4	7/251 (2.79%)	7
Leukopenia ^† 1	4/254 (1.57%)	4	5/251 (1.99%)	7
Lymphadenitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Lymphadenopathy ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lymphopenia ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Neutropenia ^† 1	14/254 (5.51%)	15	22/251 (8.76%)	24
Neutrophilia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Pancytopenia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Thrombocytopenia ^† 1	3/254 (1.18%)	4	1/251 (0.40%)	1
Cardiac disorders
Atrial fibrillation ^† 1	4/254 (1.57%)	4	5/251 (1.99%)	5
Bradycardia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Bundle branch block left ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Cardiac failure ^† 1	1/254 (0.39%)	1	5/251 (1.99%)	5
Cardiac ventricular thrombosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Cardiomegaly ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Diastolic dysfunction ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Left ventricular dysfunction ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Mitral valve incompetence ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Palpitations ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pericardial effusion ^† 1	3/254 (1.18%)	3	0/251 (0.00%)	0
Sinus tachycardia ^† 1	3/254 (1.18%)	4	0/251 (0.00%)	0
Tachycardia ^† 1	7/254 (2.76%)	8	4/251 (1.59%)	4
Ear and labyrinth disorders
Cerumen impaction ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Deafness ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Ear pain ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Hypoacusis ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Tinnitus ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Vertigo ^† 1	6/254 (2.36%)	6	8/251 (3.19%)	8
Endocrine disorders
Goitre ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hyperthyroidism ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Oestrogen deficiency ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Eye disorders
Cataract ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Chorioretinopathy ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Conjunctival irritation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Conjunctivitis allergic ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Diplopia ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Dry eye ^† 1	1/254 (0.39%)	1	4/251 (1.59%)	4
Eye discharge ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Eye irritation ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
Eye pain ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Eyelid oedema ^† 1	0/254 (0.00%)	0	10/251 (3.98%)	10
Eyelid skin dryness ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hypermetropia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Keratitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lacrimation increased ^† 1	13/254 (5.12%)	13	16/251 (6.37%)	16
Macular oedema ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Ocular discomfort ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Ocular hyperaemia ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Ocular icterus ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Optic nerve compression ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Periorbital oedema ^† 1	0/254 (0.00%)	0	11/251 (4.38%)	11
Photopsia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Presbyopia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Retinal vascular disorder ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Retinal vein thrombosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Retinopathy ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Ulcerative keratitis ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Vision blurred ^† 1	4/254 (1.57%)	4	8/251 (3.19%)	8
Visual acuity reduced ^† 1	3/254 (1.18%)	3	3/251 (1.20%)	3
Visual impairment ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
Gastrointestinal disorders
Abdominal discomfort ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
Abdominal distension ^† 1	3/254 (1.18%)	3	3/251 (1.20%)	3
Abdominal pain ^† 1	19/254 (7.48%)	25	23/251 (9.16%)	25
Abdominal pain lower ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Abdominal pain upper ^† 1	11/254 (4.33%)	12	12/251 (4.78%)	13
Anal fissure ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Anal haemorrhage ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Anal inflammation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Aphthous ulcer ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Ascites ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Colitis ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Constipation ^† 1	47/254 (18.50%)	57	39/251 (15.54%)	43
Defaecation urgency ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Dental caries ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Diarrhoea ^† 1	86/254 (33.86%)	126	149/251 (59.36%)	234
Diverticulum ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Dry mouth ^† 1	1/254 (0.39%)	1	15/251 (5.98%)	16
Duodenitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Dyspepsia ^† 1	12/254 (4.72%)	14	14/251 (5.58%)	14
Dysphagia ^† 1	5/254 (1.97%)	6	8/251 (3.19%)	8
Enteritis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Eructation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Flatulence ^† 1	2/254 (0.79%)	2	2/251 (0.80%)	2
Gastritis ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Gastrointestinal inflammation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Gastrointestinal motility disorder ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Gastrointestinal pain ^† 1	2/254 (0.79%)	2	2/251 (0.80%)	2
Gastrooesophageal reflux disease ^† 1	2/254 (0.79%)	3	8/251 (3.19%)	8
Glossodynia ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Haematochezia ^† 1	2/254 (0.79%)	3	1/251 (0.40%)	1
Haemorrhoids ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
Hiatus hernia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hyperchlorhydria ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hypoaesthesia oral ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Lip blister ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lip dry ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lower gastrointestinal haemorrhage ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Melaena ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Mouth ulceration ^† 1	2/254 (0.79%)	2	4/251 (1.59%)	4
Nausea ^† 1	62/254 (24.41%)	81	94/251 (37.45%)	117
Odynophagia ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Oesophageal pain ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Oesophagitis ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Oral discomfort ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Oral dysaesthesia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Oral pain ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Paraesthesia oral ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Rectal haemorrhage ^† 1	2/254 (0.79%)	2	3/251 (1.20%)	3
Rectal tenesmus ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Stomatitis ^† 1	33/254 (12.99%)	38	65/251 (25.90%)	82
Swollen tongue ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Tooth loss ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Toothache ^† 1	3/254 (1.18%)	3	1/251 (0.40%)	1
Upper gastrointestinal haemorrhage ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Vomiting ^† 1	31/254 (12.20%)	40	64/251 (25.50%)	87
General disorders
Asthenia ^† 1	46/254 (18.11%)	54	66/251 (26.29%)	76
Catheter site inflammation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Chest pain ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Chills ^† 1	3/254 (1.18%)	3	6/251 (2.39%)	6
Device failure ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Extravasation ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Face oedema ^† 1	4/254 (1.57%)	4	22/251 (8.76%)	26
Fatigue ^† 1	78/254 (30.71%)	96	69/251 (27.49%)	97
Feeling cold ^† 1	1/254 (0.39%)	2	1/251 (0.40%)	1
Feeling hot ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Gait disturbance ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
General physical health deterioration ^† 1	3/254 (1.18%)	4	0/251 (0.00%)	0
Generalised oedema ^† 1	0/254 (0.00%)	0	8/251 (3.19%)	8
Hyperthermia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Inflammation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Inflammatory pain ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Influenza like illness ^† 1	9/254 (3.54%)	10	2/251 (0.80%)	2
Infusion site extravasation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Injection site pruritus ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Injection site reaction ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Local swelling ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Localised oedema ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Malaise ^† 1	4/254 (1.57%)	4	1/251 (0.40%)	1
Mucosal inflammation ^† 1	2/254 (0.79%)	3	9/251 (3.59%)	10
Mucosal toxicity ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Nodule ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Non-cardiac chest pain ^† 1	5/254 (1.97%)	6	7/251 (2.79%)	7
Oedema ^† 1	7/254 (2.76%)	7	13/251 (5.18%)	14
Oedema peripheral ^† 1	38/254 (14.96%)	40	75/251 (29.88%)	98
Pain ^† 1	4/254 (1.57%)	4	9/251 (3.59%)	10
Performance status decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Peripheral swelling ^† 1	3/254 (1.18%)	3	6/251 (2.39%)	9
Pyrexia ^† 1	31/254 (12.20%)	42	47/251 (18.73%)	62
Soft tissue inflammation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Temperature intolerance ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Tenderness ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Xerosis ^† 1	2/254 (0.79%)	2	2/251 (0.80%)	2
Hepatobiliary disorders
Bile duct obstruction ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Cholecystitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Cholestasis ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Hepatic function abnormal ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hepatic pain ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hepatocellular injury ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Hydrocholecystis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hyperbilirubinaemia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	2
Jaundice ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Immune system disorders
Contrast media allergy ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Drug hypersensitivity ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Iodine allergy ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infections and infestations
Abdominal infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Anal abscess ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Anal fungal infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Anal infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Angular cheilitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Aspergillus infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Bacterial infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Bacteriuria ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Breast abscess ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Bronchitis ^† 1	7/254 (2.76%)	8	8/251 (3.19%)	9
Bullous impetigo ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Candida infection ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Cellulitis ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Clostridial infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Clostridium difficile infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Conjunctivitis ^† 1	5/254 (1.97%)	7	12/251 (4.78%)	13
Cystitis ^† 1	6/254 (2.36%)	6	3/251 (1.20%)	4
Device related infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Diverticulitis ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Ear infection ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Erysipelas ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Eye infection ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Folliculitis ^† 1	1/254 (0.39%)	1	4/251 (1.59%)	6
Fungal infection ^† 1	4/254 (1.57%)	4	1/251 (0.40%)	1
Fungal oesophagitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Fungal skin infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Gastroenteritis ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Genital infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Gingivitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Helicobacter infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Herpes simplex ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Herpes virus infection ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Herpes zoster ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Hordeolum ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Impetigo ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infected dermal cyst ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Influenza ^† 1	3/254 (1.18%)	3	3/251 (1.20%)	3
Injection site infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Localised infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lower respiratory tract infection ^† 1	7/254 (2.76%)	7	1/251 (0.40%)	1
Lung infection ^† 1	5/254 (1.97%)	6	5/251 (1.99%)	5
Mucosal infection ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Nasopharyngitis ^† 1	7/254 (2.76%)	8	10/251 (3.98%)	12
Onychomycosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Oral candidiasis ^† 1	5/254 (1.97%)	5	5/251 (1.99%)	5
Oral fungal infection ^† 1	2/254 (0.79%)	2	4/251 (1.59%)	4
Oral herpes ^† 1	2/254 (0.79%)	2	3/251 (1.20%)	4
Oral infection ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Oropharyngeal candidiasis ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Oropharyngitis fungal ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Otitis externa ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Otitis media ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Paronychia ^† 1	6/254 (2.36%)	6	14/251 (5.58%)	14
Pharyngitis ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Pharyngotonsillitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Pneumocystis jirovecii pneumonia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pneumonia ^† 1	4/254 (1.57%)	4	8/251 (3.19%)	11
Pneumonia bacterial ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Rash pustular ^† 1	3/254 (1.18%)	3	6/251 (2.39%)	8
Respiratory tract infection ^† 1	8/254 (3.15%)	10	9/251 (3.59%)	10
Respiratory tract infection viral ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Rhinitis ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Sepsis ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Sialoadenitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Sinusitis ^† 1	5/254 (1.97%)	5	6/251 (2.39%)	7
Skin candida ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Skin infection ^† 1	4/254 (1.57%)	4	1/251 (0.40%)	1
Staphylococcal infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	2
Tonsillitis ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Tonsillitis bacterial ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Tooth abscess ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	2
Upper respiratory tract infection ^† 1	8/254 (3.15%)	11	1/251 (0.40%)	1
Urinary tract infection ^† 1	6/254 (2.36%)	11	16/251 (6.37%)	21
Urinary tract infection bacterial ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Urosepsis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Vaginal infection ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Viral infection ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Viral pharyngitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Vulvovaginal candidiasis ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Vulvovaginal mycotic infection ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Injury, poisoning and procedural complications
Epiphyseal fracture ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Excoriation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Fall ^† 1	2/254 (0.79%)	2	4/251 (1.59%)	4
Foot fracture ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hip fracture ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Infusion related reaction ^† 1	4/254 (1.57%)	4	0/251 (0.00%)	0
Lumbar vertebral fracture ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Post procedural complication ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Procedural pain ^† 1	2/254 (0.79%)	3	1/251 (0.40%)	1
Procedural site reaction ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Pulmonary radiation injury ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Radiation pneumonitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Rib fracture ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Skin abrasion ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Skin injury ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Skin wound ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Ulna fracture ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Venous injury ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Wound ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Investigations
Alanine aminotransferase increased ^† 1	5/254 (1.97%)	5	6/251 (2.39%)	8
Aspartate aminotransferase increased ^† 1	3/254 (1.18%)	3	6/251 (2.39%)	7
Blood albumin decreased ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Blood alkaline phosphatase increased ^† 1	4/254 (1.57%)	4	1/251 (0.40%)	1
Blood bilirubin increased ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Blood calcium increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Blood creatine phosphokinase MB increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	6
Blood creatine phosphokinase increased ^† 1	0/254 (0.00%)	0	6/251 (2.39%)	9
Blood creatinine increased ^† 1	2/254 (0.79%)	2	6/251 (2.39%)	10
Blood glucose increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Blood lactate dehydrogenase increased ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Blood potassium decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Blood pressure decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Blood pressure increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Blood pressure systolic decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Blood thyroid stimulating hormone decreased ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Blood urea increased ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Body temperature increased ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Breath sounds abnormal ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
C-reactive protein increased ^† 1	2/254 (0.79%)	2	7/251 (2.79%)	9
Carcinoembryonic antigen increased ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Eastern Cooperative Oncology Group performance status worsened ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Ejection fraction decreased ^† 1	1/254 (0.39%)	1	5/251 (1.99%)	5
Gamma-glutamyltransferase increased ^† 1	6/254 (2.36%)	6	6/251 (2.39%)	6
Inspiratory capacity decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
International normalised ratio increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Neutrophil count decreased ^† 1	1/254 (0.39%)	2	1/251 (0.40%)	1
Neutrophil count increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Oxygen saturation decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Platelet count decreased ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	4
Platelet count increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Protein total decreased ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Transaminases increased ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Troponin I increased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	2
Troponin increased ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Urine output decreased ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Weight decreased ^† 1	11/254 (4.33%)	12	21/251 (8.37%)	21
Weight increased ^† 1	2/254 (0.79%)	2	7/251 (2.79%)	7
White blood cell count increased ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Metabolism and nutrition disorders
Abnormal loss of weight ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Cachexia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Decreased appetite ^† 1	60/254 (23.62%)	76	56/251 (22.31%)	68
Dehydration ^† 1	6/254 (2.36%)	6	11/251 (4.38%)	12
Electrolyte imbalance ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Fluid retention ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Hypercalcaemia ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Hyperglycaemia ^† 1	3/254 (1.18%)	3	2/251 (0.80%)	4
Hyperkalaemia ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Hyperphosphataemia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hyperproteinaemia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hypoalbuminaemia ^† 1	4/254 (1.57%)	4	9/251 (3.59%)	11
Hypocalcaemia ^† 1	1/254 (0.39%)	1	5/251 (1.99%)	5
Hypoglycaemia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	2
Hypokalaemia ^† 1	3/254 (1.18%)	3	11/251 (4.38%)	11
Hypomagnesaemia ^† 1	6/254 (2.36%)	10	3/251 (1.20%)	3
Hyponatraemia ^† 1	2/254 (0.79%)	2	11/251 (4.38%)	11
Hypophosphataemia ^† 1	2/254 (0.79%)	2	2/251 (0.80%)	4
Hypoproteinaemia ^† 1	3/254 (1.18%)	3	0/251 (0.00%)	0
Iron deficiency ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Magnesium deficiency ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Malnutrition ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Vitamin D deficiency ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Musculoskeletal and connective tissue disorders
Amyotrophy ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Arthralgia ^† 1	19/254 (7.48%)	23	23/251 (9.16%)	24
Axillary mass ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Back pain ^† 1	28/254 (11.02%)	32	19/251 (7.57%)	22
Bone pain ^† 1	20/254 (7.87%)	21	18/251 (7.17%)	23
Coccydynia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Fistula discharge ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Flank pain ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Fracture pain ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Groin pain ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Hypercreatinaemia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Intervertebral disc protrusion ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Joint stiffness ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Joint swelling ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Limb discomfort ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Muscle atrophy ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Muscle spasms ^† 1	7/254 (2.76%)	8	3/251 (1.20%)	3
Muscle twitching ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Muscular weakness ^† 1	7/254 (2.76%)	8	10/251 (3.98%)	10
Musculoskeletal chest pain ^† 1	12/254 (4.72%)	12	11/251 (4.38%)	11
Musculoskeletal discomfort ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Musculoskeletal pain ^† 1	13/254 (5.12%)	15	5/251 (1.99%)	5
Myalgia ^† 1	37/254 (14.57%)	49	23/251 (9.16%)	24
Myopathy ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Myositis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Neck pain ^† 1	5/254 (1.97%)	6	4/251 (1.59%)	4
Osteoarthritis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Osteonecrosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Osteopenia ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Pain in extremity ^† 1	15/254 (5.91%)	20	9/251 (3.59%)	11
Pain in jaw ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Rheumatic disorder ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Rheumatoid arthritis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Spinal pain ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Endometrial sarcoma ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Tumour associated fever ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Tumour necrosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Tumour pain ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Nervous system disorders
Ageusia ^† 1	2/254 (0.79%)	3	1/251 (0.40%)	1
Amnesia ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Aphasia ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Aphonia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Apraxia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Balance disorder ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Burning sensation ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Cerebellar syndrome ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Cerebral ischaemia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Coordination abnormal ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Disturbance in attention ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Dizziness ^† 1	10/254 (3.94%)	11	15/251 (5.98%)	15
Dizziness postural ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Dysarthria ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Dysgeusia ^† 1	23/254 (9.06%)	25	17/251 (6.77%)	17
Extrapyramidal disorder ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Facial neuralgia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Headache ^† 1	26/254 (10.24%)	30	9/251 (3.59%)	10
Hyperaesthesia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hypersomnia ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Hypoaesthesia ^† 1	3/254 (1.18%)	5	1/251 (0.40%)	1
Lethargy ^† 1	5/254 (1.97%)	5	1/251 (0.40%)	1
Memory impairment ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Monoparesis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Neuralgia ^† 1	5/254 (1.97%)	5	0/251 (0.00%)	0
Neuropathy peripheral ^† 1	10/254 (3.94%)	10	12/251 (4.78%)	12
Neurotoxicity ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Paraesthesia ^† 1	17/254 (6.69%)	23	18/251 (7.17%)	18
Paresis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Parosmia ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Partial seizures ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Peripheral motor neuropathy ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Peripheral sensorimotor neuropathy ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Peripheral sensory neuropathy ^† 1	7/254 (2.76%)	9	9/251 (3.59%)	9
Polyneuropathy ^† 1	5/254 (1.97%)	5	4/251 (1.59%)	4
Psychomotor hyperactivity ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Sciatica ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Seizure ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Somnolence ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Syncope ^† 1	0/254 (0.00%)	0	6/251 (2.39%)	7
VIIth nerve paralysis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Vocal cord paralysis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Psychiatric disorders
Abnormal dreams ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Agitation ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Anxiety ^† 1	5/254 (1.97%)	5	10/251 (3.98%)	10
Confusional state ^† 1	3/254 (1.18%)	3	5/251 (1.99%)	6
Delusion ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Depression ^† 1	4/254 (1.57%)	4	4/251 (1.59%)	4
Disorientation ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Hallucination ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Illusion ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Insomnia ^† 1	10/254 (3.94%)	11	9/251 (3.59%)	9
Irritability ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Panic attack ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Sleep disorder ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Stress ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Tension ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Chromaturia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Chronic kidney disease ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	2
Costovertebral angle tenderness ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Cystitis noninfective ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Dysuria ^† 1	1/254 (0.39%)	1	4/251 (1.59%)	4
Haematuria ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Haemoglobinuria ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Micturition urgency ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Pollakiuria ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Proteinuria ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	3
Renal failure ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Strangury ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Urinary incontinence ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Urinary retention ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
Urinary tract pain ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Urine odour abnormal ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Reproductive system and breast disorders
Acquired hydrocele ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Breast discomfort ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Dysmenorrhoea ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Erectile dysfunction ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Pelvic pain ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Polymenorrhoea ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Prostatism ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pruritus genital ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Vaginal discharge ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Asthma ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Atelectasis ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Bronchial secretion retention ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Bronchospasm ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	2
Chronic obstructive pulmonary disease ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Cough ^† 1	35/254 (13.78%)	44	37/251 (14.74%)	39
Dry throat ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Dysphonia ^† 1	7/254 (2.76%)	7	11/251 (4.38%)	12
Dyspnoea ^† 1	40/254 (15.75%)	41	55/251 (21.91%)	57
Dyspnoea at rest ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Dyspnoea exertional ^† 1	7/254 (2.76%)	7	6/251 (2.39%)	6
Epistaxis ^† 1	8/254 (3.15%)	10	13/251 (5.18%)	13
Haemoptysis ^† 1	8/254 (3.15%)	14	8/251 (3.19%)	12
Hiccups ^† 1	2/254 (0.79%)	2	3/251 (1.20%)	3
Hypoxia ^† 1	3/254 (1.18%)	3	2/251 (0.80%)	2
Increased bronchial secretion ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Interstitial lung disease ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Laryngeal inflammation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Lung consolidation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Lung infiltration ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Nasal congestion ^† 1	4/254 (1.57%)	4	2/251 (0.80%)	2
Nasal discomfort ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Oropharyngeal pain ^† 1	8/254 (3.15%)	8	7/251 (2.79%)	8
Pleural disorder ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pleural effusion ^† 1	9/254 (3.54%)	12	11/251 (4.38%)	14
Pleuritic pain ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Pneumonitis ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Pneumothorax ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Productive cough ^† 1	10/254 (3.94%)	11	8/251 (3.19%)	8
Pulmonary congestion ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pulmonary embolism ^† 1	1/254 (0.39%)	1	3/251 (1.20%)	3
Pulmonary haemorrhage ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Pulmonary oedema ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pulmonary pain ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Rales ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Respiratory distress ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Respiratory failure ^† 1	2/254 (0.79%)	2	2/251 (0.80%)	2
Rhinitis allergic ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Rhinorrhoea ^† 1	6/254 (2.36%)	7	5/251 (1.99%)	5
Rhonchi ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Sinus congestion ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Sleep apnoea syndrome ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Throat irritation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Upper respiratory tract inflammation ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Upper-airway cough syndrome ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Wheezing ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Skin and subcutaneous tissue disorders
Acne ^† 1	2/254 (0.79%)	2	7/251 (2.79%)	7
Alopecia ^† 1	64/254 (25.20%)	65	49/251 (19.52%)	49
Blister ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Dermatitis ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Dermatitis acneiform ^† 1	2/254 (0.79%)	2	30/251 (11.95%)	34
Dermatitis bullous ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Dermatitis diaper ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Dry skin ^† 1	14/254 (5.51%)	19	30/251 (11.95%)	31
Eczema ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	3
Erythema ^† 1	8/254 (3.15%)	8	7/251 (2.79%)	7
Erythema multiforme ^† 1	0/254 (0.00%)	0	4/251 (1.59%)	4
Exfoliative rash ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hand dermatitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hyperhidrosis ^† 1	4/254 (1.57%)	4	2/251 (0.80%)	2
Hyperkeratosis ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Hypertrichosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Ingrowing nail ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Nail bed disorder ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Nail bed inflammation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Nail discolouration ^† 1	5/254 (1.97%)	5	8/251 (3.19%)	8
Nail disorder ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Nail ridging ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Nail toxicity ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Night sweats ^† 1	2/254 (0.79%)	3	0/251 (0.00%)	0
Onychalgia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Onychoclasis ^† 1	3/254 (1.18%)	3	4/251 (1.59%)	4
Onycholysis ^† 1	7/254 (2.76%)	7	12/251 (4.78%)	12
Onychomadesis ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Pain of skin ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Palmar-plantar erythrodysaesthesia syndrome ^† 1	2/254 (0.79%)	2	7/251 (2.79%)	7
Petechiae ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Photosensitivity reaction ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Pigmentation disorder ^† 1	2/254 (0.79%)	2	0/251 (0.00%)	0
Pruritus ^† 1	12/254 (4.72%)	12	16/251 (6.37%)	21
Pruritus generalised ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	3
Psoriasis ^† 1	2/254 (0.79%)	2	1/251 (0.40%)	1
Rash ^† 1	28/254 (11.02%)	29	85/251 (33.86%)	114
Rash erythematous ^† 1	2/254 (0.79%)	2	7/251 (2.79%)	10
Rash generalised ^† 1	0/254 (0.00%)	0	4/251 (1.59%)	4
Rash macular ^† 1	2/254 (0.79%)	2	7/251 (2.79%)	10
Rash maculo-papular ^† 1	0/254 (0.00%)	0	8/251 (3.19%)	9
Rash papular ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Rash pruritic ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Scar pain ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Skin discolouration ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Skin exfoliation ^† 1	3/254 (1.18%)	4	2/251 (0.80%)	2
Skin fissures ^† 1	0/254 (0.00%)	0	5/251 (1.99%)	5
Skin hyperpigmentation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Skin hypopigmentation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Skin irritation ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Skin plaque ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Skin toxicity ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	3
Skin ulcer ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Solar dermatitis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Swelling face ^† 1	0/254 (0.00%)	0	3/251 (1.20%)	3
Telangiectasia ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Urticaria ^† 1	0/254 (0.00%)	0	2/251 (0.80%)	2
Vascular disorders
Deep vein thrombosis ^† 1	2/254 (0.79%)	2	2/251 (0.80%)	2
Embolism ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Flushing ^† 1	2/254 (0.79%)	2	3/251 (1.20%)	3
Haematoma ^† 1	4/254 (1.57%)	4	2/251 (0.80%)	2
Haemorrhage ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Hot flush ^† 1	5/254 (1.97%)	5	0/251 (0.00%)	0
Hypertension ^† 1	3/254 (1.18%)	5	4/251 (1.59%)	5
Hypotension ^† 1	8/254 (3.15%)	8	13/251 (5.18%)	16
Inferior vena cava syndrome ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Jugular vein thrombosis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Lymphoedema ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Orthostatic hypotension ^† 1	1/254 (0.39%)	1	2/251 (0.80%)	2
Peripheral coldness ^† 1	1/254 (0.39%)	1	1/251 (0.40%)	1
Phlebitis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Thrombophlebitis superficial ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Thrombosis ^† 1	1/254 (0.39%)	1	0/251 (0.00%)	0
Varicose vein ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
Vena cava thrombosis ^† 1	0/254 (0.00%)	0	1/251 (0.40%)	1
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.

Results Point of Contact

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Name/Title:	Dr Gabriella Mariani
Organization:	AstraZeneca Research and Development
Phone:	+44 (0)1763 263801
EMail:	ClinicalTrialTransparency@astrazeneca.com

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

Janne PA, van den Heuvel MM, Barlesi F, Cobo M, Mazieres J, Crino L, Orlov S, Blackhall F, Wolf J, Garrido P, Poltoratskiy A, Mariani G, Ghiorghiu D, Kilgour E, Smith P, Kohlmann A, Carlile DJ, Lawrence D, Bowen K, Vansteenkiste J. Selumetinib Plus Docetaxel Compared With Docetaxel Alone and Progression-Free Survival in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer: The SELECT-1 Randomized Clinical Trial. JAMA. 2017 May 9;317(18):1844-1853. doi: 10.1001/jama.2017.3438.

Janne PA, Mann H, Ghiorghiu D. Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non-Small Cell Lung Cancer (SELECT-1). Clin Lung Cancer. 2016 Mar;17(2):e1-4. doi: 10.1016/j.cllc.2015.12.010. Epub 2015 Dec 30.

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Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01933932
Other Study ID Numbers:	D1532C00079 2013-001676-38 ( EudraCT Number )
First Submitted:	August 29, 2013
First Posted:	September 2, 2013
Results First Submitted:	February 27, 2017
Results First Posted:	August 29, 2017
Last Update Posted:	October 17, 2023

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