Monotherapy: Radiological progression-free survival and overall survival data with LYNPARZA in HRRm mCRPC (including BRCAm) in the PROfound trial1,2

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PROfound examined the efficacy of LYNPARZA vs investigator’s choice of enza or abi1

See the Full PROfound Study Design

In patients with BRCA1/2- or ATM-mutated mCRPC (Cohort A)

LYNPARZA demonstrated superior rPFS vs investigator’s choice of enza or abi1

rPFS in Cohort A

rPFS in Cohort A mCRPC Efficacy Graph rPFS in Cohort A mCRPC Efficacy Graph

rPFS in Cohort A: Determined by BICR using RECIST version 1.1 and PCWG3 (bone) criteria.

Events, n (%): 106/162 (65) with LYNPARZA and 68/83 (82) with investigator’s choice of enzalutamide or abiraterone.

Consistent results were observed in exploratory analyses of rPFS:

  • – For patients who received or did not receive prior taxane therapy
  • – For those with germline BRCA mutations identified using the Myriad BRACAnalysis CDx® assay compared with those with BRCA mutations identified using the Foundation Medicine F1CDx assay

Exploratory subgroup analysis

rPFS in patients with BRCAm mCRPC3-5

rPFS in exploratory BRCAm subgroup

rPFS BRCAm mCRPC Efficacy 78 Graph rPFS BRCAm mCRPC Efficacy 78 Graph

Exploratory subgroup analyses:

Exploratory analyses are descriptive only. The PROfound trial was not designed to assess statistical significance in rPFS between treatment arms in the BRCAm or ATM-mutated subgroups. Results should be interpreted with caution.

rPFS in patients with BRCAm mCPRC

Events, n (%): 62/102 (60.8) with LYNPARZA and 51/58 (87.9) with investigator's choice of enzalutamide or abiraterone.

rPFS in patients with ATMm mCRPC

Events, n (%): 46/62 (74.2) with LYNPARZA and 17/24 (70.8) with investigator’s choice of enzalutamide or abiraterone: 4% increased risk of progression or death; HR=1.04 (95% CI: 0.61–1.87).

In patients with BRCA1/2- or ATM-mutated mCRPC (Cohort A)

LYNPARZA demonstrated superior overall survival vs investigator’s choice of enza or abi1,2

OS in Cohort A

OS in Cohort A mCRPC Efficacy 31 Graph OS in Cohort A mCRPC Efficacy 31 Graph

OS in Cohort A: LYNPARZA demonstrated an OS benefit vs investigator’s choice of enzalutamide or abiraterone.

Events, n (%): 91/162 (56) with LYNPARZA and 57/83 (69) with investigator’s choice of enzalutamide or abiraterone.

PROfound was powered to evaluate several secondary endpoints within a hierarchical statistical analysis, including:

  • •ORR in Cohort A
  • •rPFS in Cohort A+B
  • •OS in Cohort A

Exploratory subgroup analysis

Overall survival in patients with BRCAm mCRPC3-6

OS in exploratory BRCAm subgroup

OS in BRCAm Efficacy 37 Graph OS in BRCAm Efficacy 37 Graph

Exploratory subgroup analyses:

These exploratory subgroup analyses are descriptive only. The PROfound trial was not designed to assess statistical significance in OS between the treatment arms in the BRCAm or ATM-mutated subgroups. Results should be interpreted with caution.

OS in patients with BRCAm mCRPC

Events, n (%): 53/102 (52) with LYNPARZA and 41/58 (70.7) with investigator's choice of enzalutamide or abiraterone.

OS in patients with ATM mCRPC

Events, n (%): 39/62 (62.9) with LYNPARZA and 15/24 (62.5) with investigator's choice of enzalutamide or abiraterone: 7% reduced risk of death; HR=0.93 (95% CI: 0.53–1.75).

In patients with HRRm mCRPC (Cohort A+B)

LYNPARZA demonstrated superior rPFS vs investigator’s choice of enza or abi1,2

rPFS in Cohort A + B

rPFS in Cohort A + B mCRPC Efficacy 51 Graph rPFS in Cohort A + B mCRPC Efficacy 51 Graph

rPFS in Cohort A+B was assessed by BICR.

Genes included in Cohort A+B:

BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A,* RAD51B, RAD51C, RAD51D, and RAD54L.

  • *Although patients with PPP2R2A mutations were included in all analyses of Cohort A+B, LYNPARZA is not indicated for this population due to an unfavorable risk-benefit.

PROfound was powered to evaluate several secondary endpoints within a hierarchical statistical analysis, including:

  • •ORR in Cohort A
  • •rPFS in Cohort A+B
  • •OS in Cohort A

Select Secondary Endpoint: ORR in Cohort A

LYNPARZA significantly improved confirmed ORR as assessed by BICR vs investigator’s choice of enzalutamide or abiraterone for patients with measurable disease at baseline: 33% (n=28/84) with LYNPARZA (95% CI: 23–45, P <0.0001) vs 2% (n=1/43) with investigator’s choice of enzalutamide or abiraterone (95% CI: 0–12, P<0.0001)

Gene mutations included in Cohort A: BRCA1, BRCA2, and/or ATM

PROfound was a phase 3 trial in patients with HRRm mCRPC (including BRCAm)

LYNPARZA Study Design PROfound Trial Chart LYNPARZA Study Design PROfound Trial Chart

Primary endpoint:

Cohort A: Radiological progression-free survival (rPFS) as determined by BICR using RECIST v 1.1 and PCWG3 (bone) criteria.

Select secondary endpoints (tested sequentially within a hierarchical statistical analysis):

  • • Cohort A: Confirmed objective response rate (ORR)
  • • Cohorts A+B: rPFS as assessed by BICR
  • • Cohort A: Overall survival (OS)

Treatment was continued until objective radiological disease progression determined by BICR.

Patients with mCRPC were eligible for PROfound regardless of previous taxane use.

Although patients with PPP2R2A gene mutations were enrolled in the trial, LYNPARZA is not indicated for the treatment of patients with this gene mutation due to unfavorable risk-benefit.

  • *HRR gene mutations (BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and/or RAD54L) were identified by tissue-based testing using the Foundation Medicine FoundationOne® clinical trial HRR assay performed at a central laboratory. No patients were enrolled who had mutations in 2 of the 15 prespecified HRR genes: FANCL and RAD51C.
  • †Patients with co-mutations (BRCA1, BRCA2, or ATM plus a Cohort B gene) were assigned to Cohort A.
  • ‡All patients received a GnRH analog or had prior bilateral orchiectomy.
  • §BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L.
  • ||Upon radiological progression confirmed by BICR, patients randomized to enzalutamide or abiraterone were given the option to switch to LYNPARZA.