Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)

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ClinicalTrials.gov Identifier: NCT02987543

Recruitment Status : Completed

First Posted : December 9, 2016

Results First Posted : October 12, 2020

Last Update Posted : October 6, 2023

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Sponsor:

Collaborators:

Merck Sharp & Dohme LLC

Foundation Medicine, Inc.

Myriad Genetics, Inc.

Information provided by (Responsible Party):

AstraZeneca

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Metastatic Castration-resistant Prostate Cancer
Interventions	Drug: olaparib Drug: enzalutamide Drug: abiraterone acetate
Enrollment	387

Participant Flow

Recruitment Details	Subjects were divided into two cohorts based on HRR gene mutation status. Subjects with mutations in either BRCA1, BRCA2, or ATM are in Cohort A whereas subjects with mutations among 12 other genes involved in the HRR pathway (BARD1, BRIP1, CDK12, CHEK1,CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L) are in Cohort B.
Pre-assignment Details


Arm/Group Title	Cohort A Olaparib 300mg bd	Cohort A Investigators Choice of NHA	Cohort B Olaparib 300mg bd	Cohort B Investigators Choice of NHA
Arm/Group Description	2x150mg film-coated tablets	either enzalutamide capsules (160 m...	2x150mg film-coated tablets	either enzalutamide capsules (160 m...
Arm/Group Description	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Period Title: Overall Study
Started	162	83	94	48
Completed	0	0	0	0
Not Completed	162	83	94	48
Reason Not Completed
Ongoing study at data cut off	49	21	19	12
Death	88	54	67	28
Lost to Follow-up	3	0	1	0
Screen failure	0	0	0	1
Withdrawal by Subject	21	7	7	6
Study terminated by sponsor	1	0	0	0
Investigator decision	0	1	0	0
Disease progression	0	0	0	1

Baseline Characteristics

Arm/Group Title		Cohort A Olaparib 300mg bd	Cohort A Investigators Choice of NHA	Cohort B Olaparib 300mg bd	Cohort B Investigators Choice of NHA	Total
Arm/Group Description		2x150mg film-coated tablets	either enzalutamide capsules (160 m...	2x150mg film-coated tablets	either enzalutamide capsules (160 m...	Total of all reporting groups
Arm/Group Description		2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)	Total of all reporting groups
Overall Number of Baseline Participants		162	83	94	48	387
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	162 participants	83 participants	94 participants	48 participants	387 participants
		68.0 (8.23)	68.1 (7.36)	69.2 (8.79)	70.3 (7.83)	68.6 (8.15)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	162 participants	83 participants	94 participants	48 participants	387 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	162 100.0%	83 100.0%	94 100.0%	48 100.0%	387 100.0%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	162 participants	83 participants	94 participants	48 participants	387 participants
White		109	55	54	30	248
Black or African American		2	1	5	0	8
Asian		43	19	26	17	105
Other		1	1	1	0	3
Missing		7	7	8	1	23

Outcome Measures

1.Primary Outcome


Title	Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A Only
Description	The time from randomisation until the date of objective radiological d...
Description	The time from randomisation until the date of objective radiological disease progression (determined by RECIST 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG-3) (bone)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression. Progression is defined using (i) Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue, as a >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters; (ii) Prostate Cancer Working Group 3 (PGWG-3) for bone as >= 2 new bone lesions on the 1st week 8 scan compared to baseline. The confirmatory scan, >=6 weeks later, must show >=2 more new bone lesions (for a total of >=4 new bone lesions since baseline).
Time Frame	Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).

Outcome Measure Data

Analysis Population Description

Full Analysis Set


Arm/Group Title	Cohort A Olaparib 300mg bd	Cohort A Investigators Choice of NHA
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 m...
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Overall Number of Participants Analyzed	162	83
Median (95% Confidence Interval) Unit of Measure: Months
	7.39 (6.24 to 9.33)	3.55 (1.91 to 3.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A Olaparib 300mg bd, Cohort A Investigators Choice of NHA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95% 0.25 to 0.47
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Confirmed Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) - Cohort A Only
Description	ORR is the percentage of patients with at least one visit response of ...
Description	ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = >=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.
Time Frame	Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).

Outcome Measure Data

Analysis Population Description

Evaluable for response


Arm/Group Title	Cohort A Olaparib 300mg bd	Cohort A Investigators Choice of NHA
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 m...
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Overall Number of Participants Analyzed	84	43
Measure Type: Count of Participants Unit of Measure: Participants
Response	28 33.3%	1 2.3%
No response	56 66.7%	42 97.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A Olaparib 300mg bd, Cohort A Investigators Choice of NHA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	20.86
	Confidence Interval	(2-Sided) 95% 4.18 to 379.18
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Radiological Progression Free Survival (rPFS) by Blinded Independent Central Review (BICR) - Cohort A+B
Description	The time from randomisation until the date of objective radiological d...
Description	The time from randomisation until the date of objective radiological disease progression (by RECIST 1.1 and Prostate Cancer Working Group 3 (PGWG-3)) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
Time Frame	Tumor assessments every 8 weeks from randomisation until radiographic progression assessed by BICR (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).

Outcome Measure Data

Analysis Population Description

Full Analysis Set


Arm/Group Title	Cohort A Olaparib 300mg bd	Cohort A Investigators Choice of NHA
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 m...
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Overall Number of Participants Analyzed	256	131
Median (95% Confidence Interval) Unit of Measure: Months
	5.82 (5.52 to 7.36)	3.52 (2.2 to 3.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A Olaparib 300mg bd, Cohort A Investigators Choice of NHA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.49
	Confidence Interval	(2-Sided) 95% 0.38 to 0.63
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Time to Pain Progression - Cohort A Only
Description	Time from randomisation to time point at which worsening in pain is ob...
Description	Time from randomisation to time point at which worsening in pain is observed (ie date of pain progression - date of randomisation + 1). Based on average Brief Pain Inventory - short form (BPI-SF) worst pain [Item 3] and Analgesic Quantification Algorithm [AQA] score.
Time Frame	Every 4 weeks from randomisation (for 7 consecutive days) throughout the study (median duration of treatment of 7 and 4 months for Olaparib and Investigators Choice of NHA respectively).

Outcome Measure Data

Analysis Population Description

Full Analysis Set


Arm/Group Title	Cohort A Olaparib 300mg bd	Cohort A Investigators Choice of NHA
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 m...
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Overall Number of Participants Analyzed	162	83
Median (95% Confidence Interval) Unit of Measure: Months
	NA ^[1] (NA to NA)	9.92 ^[1] (5.39 to NA)

[1]

NA - Not calculated, estimates cannot be calculated due to too few events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A Olaparib 300mg bd, Cohort A Investigators Choice of NHA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0192
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95% 0.22 to 0.91
	Estimation Comments	[Not Specified]

5.Secondary Outcome


Title	Overall Survival (OS) - Cohort A Only
Description	Number of Participants with Overall Survival (OS) - Cohort A only.
Description	Number of Participants with Overall Survival (OS) - Cohort A only.
Time Frame	Approximately 35 months after the first patient was randomised.

Outcome Measure Data

Analysis Population Description

Full analysis set


Arm/Group Title	Cohort A Olaparib 300mg bd	Cohort A Investigators Choice of NHA
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 m...
Arm/Group Description:	2x150mg film-coated tablets	either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
Overall Number of Participants Analyzed	162	83
Measure Type: Count of Participants Unit of Measure: Participants
Died	91 56.2%	57 68.7%
Alive at data cut-off	49 30.2%	21 25.3%
Terminated prior to death (withdrawn consent)	22 13.6%	5 6.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cohort A Olaparib 300mg bd, Cohort A Investigators Choice of NHA
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0175
	Comments	2-sided p-value
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95% 0.50 to 0.97
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From the time of signature of informed consent throughout the treatment period (median duration of treatment of 7.5 and 3.9 months for Olaparib and Investigators Choice of NHA respectively) up to and including the 30-day follow-up period
Adverse Event Reporting Description	There were 131 subjects randomised to the Investigators Choice of NHA treatment group (Full Analysis Set), however 1 of these subjects did not receive treatment (resulting in 130 in the Safety Analysis Set). Hence, for the Investigators Choice of NHA, the Total number at risk for all-cause mortality = 131 while the Total # at Risk by any Serious Adverse Event = 130 and the Total # at Risk by any Other Adverse Event = 130.

Arm/Group Title	Cohort A+B Olaparib 300mg bd		Cohort A+B Investigators Choice of NHA
Arm/Group Description	2x150mg film-coated tablets		either enzalutamide capsules (160 m...
Arm/Group Description	2x150mg film-coated tablets		either enzalutamide capsules (160 mg od) or abiraterone acetate tablets (1,000 mg od with 5 mg bid prednisone)
All-Cause Mortality
	Cohort A+B Olaparib 300mg bd		Cohort A+B Investigators Choice of NHA
	Affected / at Risk (%)		Affected / at Risk (%)
Total	160/256 (62.50%)		88/131 (67.18%)
Serious Adverse Events Serious Adverse Events
	Cohort A+B Olaparib 300mg bd		Cohort A+B Investigators Choice of NHA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	94/256 (36.72%)		39/130 (30.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	23/256 (8.98%)	24	0/130 (0.00%)	0
Febrile neutropenia ^† 1	1/256 (0.39%)	1	1/130 (0.77%)	1
Neutropenia ^† 1	3/256 (1.17%)	3	0/130 (0.00%)	0
Pancytopenia ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Thrombocytopenia ^† 1	4/256 (1.56%)	6	0/130 (0.00%)	0
Cardiac disorders
Acute coronary syndrome ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Angina pectoris ^† 1	1/256 (0.39%)	1	2/130 (1.54%)	2
Atrial fibrillation ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Cardiac failure ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Cardiac failure acute ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Cardiomyopathy ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Cardiopulmonary failure ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
Coronary ostial stenosis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Myocardial infarction ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Right ventricular failure ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Coronary artery stenosis ^† 2	0/256 (0.00%)	0	1/130 (0.77%)	1
Endocrine disorders
Adrenal insufficiency ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Eye disorders
Diplopia ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Diarrhoea ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Diverticulum intestinal ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Gastric perforation ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Gastric ulcer ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Gastric ulcer haemorrhage ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Inguinal hernia ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Nausea ^† 1	2/256 (0.78%)	2	2/130 (1.54%)	2
Obstruction gastric ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Obstructive pancreatitis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Small intestinal obstruction ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Stress ulcer ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Vomiting ^† 1	4/256 (1.56%)	4	1/130 (0.77%)	1
Duodenal ulcer perforation ^† 2	0/256 (0.00%)	0	1/130 (0.77%)	1
General disorders
Asthenia ^† 1	4/256 (1.56%)	4	1/130 (0.77%)	1
Death ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Fatigue ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
General physical health deterioration ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Pain ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Pyrexia ^† 1	3/256 (1.17%)	3	2/130 (1.54%)	3
Sudden death ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Hepatobiliary disorders
Budd-Chiari syndrome ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Cholangitis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Cholecystitis acute ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Infections and infestations
Anal abscess ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Cellulitis of male external genital organ ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Cystitis ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Gastroenteritis ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Infection ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Nasopharyngitis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Neutropenic sepsis ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Pharyngitis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Pneumonia ^† 1	11/256 (4.30%)	13	4/130 (3.08%)	4
Pyelonephritis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Sepsis ^† 1	3/256 (1.17%)	3	3/130 (2.31%)	3
Septic shock ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Urinary tract infection ^† 1	5/256 (1.95%)	6	4/130 (3.08%)	4
Urosepsis ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Pneumocystis jirovecii pneumoni ^† 2	1/256 (0.39%)	1	0/130 (0.00%)	0
Injury, poisoning and procedural complications
Ankle fracture ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Concussion ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Cystitis radiation ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Fall ^† 1	1/256 (0.39%)	1	2/130 (1.54%)	2
Femur fracture ^† 1	3/256 (1.17%)	3	0/130 (0.00%)	0
Fracture ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Gastroenteritis radiation ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Post-traumatic pain ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Spinal compression fracture ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Spinal fracture ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Subdural haematoma ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Metabolism and nutrition disorders
Decreased appetite ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
Dehydration ^† 1	0/256 (0.00%)	0	3/130 (2.31%)	3
Hypocalcaemia ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Hypoglycaemia ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Hyponatraemia ^† 1	2/256 (0.78%)	3	0/130 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Back pain ^† 1	1/256 (0.39%)	1	1/130 (0.77%)	1
Bone pain ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
Muscular weakness ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
Musculoskeletal chest pain ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
Musculoskeletal pain ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Spinal stenosis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Glioma ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Transitional cell carcinoma ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Nervous system disorders
Ballismus ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Cerebral infarction ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Cerebrovascular accident ^† 1	3/256 (1.17%)	3	0/130 (0.00%)	0
Dizziness ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Ischaemic stroke ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Neuralgia ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Spinal cord compression ^† 1	1/256 (0.39%)	1	1/130 (0.77%)	1
Syncope ^† 2	1/256 (0.39%)	1	0/130 (0.00%)	0
Psychiatric disorders
Confusional state ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Delirium ^† 1	1/256 (0.39%)	1	2/130 (1.54%)	2
Renal and urinary disorders
Acute kidney injury ^† 1	1/256 (0.39%)	1	2/130 (1.54%)	2
Calculus bladder ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Chronic kidney disease ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Haematuria ^† 1	3/256 (1.17%)	3	1/130 (0.77%)	1
Hydronephrosis ^† 1	1/256 (0.39%)	1	1/130 (0.77%)	1
Nephrolithiasis ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Renal failure ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Renal impairment ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Urinary retention ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
Urinary tract obstruction ^† 1	0/256 (0.00%)	0	2/130 (1.54%)	2
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease ^† 1	1/256 (0.39%)	2	0/130 (0.00%)	0
Dyspnoea ^† 1	4/256 (1.56%)	4	1/130 (0.77%)	1
Interstitial lung disease ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Pleural effusion ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Pneumonia aspiration ^† 1	3/256 (1.17%)	3	0/130 (0.00%)	0
Pneumonitis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Pneumothorax ^† 1	2/256 (0.78%)	2	0/130 (0.00%)	0
Pulmonary embolism ^† 1	5/256 (1.95%)	5	1/130 (0.77%)	1
Respiratory failure ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Skin and subcutaneous tissue disorders
Drug eruption ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Skin ulcer ^† 2	1/256 (0.39%)	1	0/130 (0.00%)	0
Vascular disorders
Arterial thrombosis ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Deep vein thrombosis ^† 1	0/256 (0.00%)	0	1/130 (0.77%)	1
Embolism ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Orthostatic hypotension ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
Phlebitis ^† 1	1/256 (0.39%)	1	0/130 (0.00%)	0
1 Term from vocabulary, MedDRA 22.0 2 Term from vocabulary, MedDRA 22.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort A+B Olaparib 300mg bd		Cohort A+B Investigators Choice of NHA
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	241/256 (94.14%)		112/130 (86.15%)
Blood and lymphatic system disorders
Anaemia ^† 1	110/256 (42.97%)	154	20/130 (15.38%)	23
Lymphopenia ^† 1	13/256 (5.08%)	15	1/130 (0.77%)	1
Neutropenia ^† 1	13/256 (5.08%)	16	0/130 (0.00%)	0
Thrombocytopenia ^† 1	18/256 (7.03%)	22	2/130 (1.54%)	2
Gastrointestinal disorders
Constipation ^† 1	49/256 (19.14%)	52	19/130 (14.62%)	21
Diarrhoea ^† 1	54/256 (21.09%)	71	9/130 (6.92%)	9
Dyspepsia ^† 1	20/256 (7.81%)	23	3/130 (2.31%)	3
Nausea ^† 1	109/256 (42.58%)	136	26/130 (20.00%)	28
Vomiting ^† 1	49/256 (19.14%)	82	17/130 (13.08%)	19
Stomatitis ^† 2	13/256 (5.08%)	14	2/130 (1.54%)	2
General disorders
Asthenia ^† 1	37/256 (14.45%)	54	18/130 (13.85%)	19
Fatigue ^† 1	68/256 (26.56%)	71	28/130 (21.54%)	28
Oedema peripheral ^† 1	34/256 (13.28%)	36	10/130 (7.69%)	10
Pyrexia ^† 1	15/256 (5.86%)	16	4/130 (3.08%)	4
Infections and infestations
Urinary tract infection ^† 1	18/256 (7.03%)	22	12/130 (9.23%)	15
Investigations
Weight decreased ^† 1	21/256 (8.20%)	21	7/130 (5.38%)	7
Metabolism and nutrition disorders
Decreased appetite ^† 1	78/256 (30.47%)	88	24/130 (18.46%)	25
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	25/256 (9.77%)	26	14/130 (10.77%)	16
Back pain ^† 1	36/256 (14.06%)	44	17/130 (13.08%)	18
Musculoskeletal chest pain ^† 1	14/256 (5.47%)	14	6/130 (4.62%)	7
Musculoskeletal pain ^† 1	17/256 (6.64%)	18	6/130 (4.62%)	6
Pain in extremity ^† 2	14/256 (5.47%)	18	6/130 (4.62%)	6
Nervous system disorders
Dizziness ^† 1	17/256 (6.64%)	18	5/130 (3.85%)	5
Dysgeusia ^† 1	18/256 (7.03%)	20	2/130 (1.54%)	2
Headache ^† 1	16/256 (6.25%)	29	3/130 (2.31%)	3
Psychiatric disorders
Insomnia ^† 1	14/256 (5.47%)	14	4/130 (3.08%)	4
Renal and urinary disorders
Haematuria ^† 1	6/256 (2.34%)	7	10/130 (7.69%)	11
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	29/256 (11.33%)	32	3/130 (2.31%)	3
Dyspnoea ^† 1	24/256 (9.38%)	25	4/130 (3.08%)	4
1 Term from vocabulary, MedDRA 22.0 2 Term from vocabulary, MedDRA 22.1 † 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 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:	Global Clinical Lead
Organization:	AstraZeneca Clinical Study Information Center
Phone:	1-877-240-9479
EMail:	information.center@astrazeneca.com

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

Roubaud G, Ozguroglu M, Penel N, Matsubara N, Mehra N, Kolinsky MP, Procopio G, Feyerabend S, Joung JY, Gravis G, Nishimura K, Gedye C, Padua C, Shore N, Thiery-Vuillemin A, Saad F, van Alphen R, Carducci MA, Desai C, Brickel N, Poehlein C, Del Rosario P, Fizazi K. Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study. Eur J Cancer. 2022 Jul;170:73-84. doi: 10.1016/j.ejca.2022.04.016. Epub 2022 May 19.

Matsubara N, Nishimura K, Kawakami S, Joung JY, Uemura H, Goto T, Kwon TG, Sugimoto M, Kato M, Wang SS, Pang ST, Chen CH, Fujita T, Nii M, Shen L, Dujka M, Hussain M, de Bono J. Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Jpn J Clin Oncol. 2022 May 5;52(5):441-448. doi: 10.1093/jjco/hyac015.

Thiery-Vuillemin A, de Bono J, Hussain M, Roubaud G, Procopio G, Shore N, Fizazi K, Dos Anjos G, Gravis G, Joung JY, Matsubara N, Castellano D, Degboe A, Gresty C, Kang J, Allen A, Poehlein C, Saad F. Pain and health-related quality of life with olaparib versus physician's choice of next-generation hormonal drug in patients with metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations (PROfound): an open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Mar;23(3):393-405. doi: 10.1016/S1470-2045(22)00017-1. Epub 2022 Feb 11. Erratum In: Lancet Oncol. 2022 Apr;23(4):e161.

Hussain M, Corcoran C, Sibilla C, Fizazi K, Saad F, Shore N, Sandhu S, Mateo J, Olmos D, Mehra N, Kolinsky MP, Roubaud G, Ozguroglu M, Matsubara N, Gedye C, Choi YD, Padua C, Kohlmann A, Huisden R, Elvin JA, Kang J, Adelman CA, Allen A, Poehlein C, de Bono J. Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib). Clin Cancer Res. 2022 Apr 14;28(8):1518-1530. doi: 10.1158/1078-0432.CCR-21-3940.

Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Ozguroglu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. doi: 10.1056/NEJMoa2022485. Epub 2020 Sep 20.

de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. doi: 10.1056/NEJMoa1911440. Epub 2020 Apr 28.

Layout table for additonal information

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT02987543
Other Study ID Numbers:	D081DC00007 2016-000300-28 ( EudraCT Number )
First Submitted:	November 15, 2016
First Posted:	December 9, 2016
Results First Submitted:	June 3, 2020
Results First Posted:	October 12, 2020
Last Update Posted:	October 6, 2023

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