1799P - Real-world (RW) treatment (tx) patterns of metastatic prostate cancer (mPCa) with enhanced access to homologous recombination repair (HRR) genomic testing and poly ADP ribose polymerase inhibitor (PARPi)

Background

Metastatic castration resistant prostate cancer (mCRPC) patients (pts) with HRR alterations (HRR⁺) benefit from PARPi. We aimed to elucidate the RW outcomes and impact of streamlined access to a biomarker driven tx approach.

Methods

In a multicentre prospective mPCa cohort study, cell free DNA next generation sequencing (cfDNA NGS) was performed using accredited assays (BC Cancer, Foundation Medicine, Alberta panel). Time to CRPC was compared between HRR⁺ and negative/unknown status (HRR⁰) using log rank test. In olaparib tx pts, ≥50% PSA decline, radiographic progression free survival (rPFS), serious adverse events (SAE), and overall survival (OS) were examined.

Results

Of 119 pts, 41 (35%) were HRR⁺ (23 BRCA2, 14 ATM, 5 CDK12, 3 CHEK2, 2 PPP2R2A, 1 BRCA1, 1 PALB2). Median age at diagnosis was 64 yrs, 45% had Gleason ≥ 8, and 13% were non-caucasian. HRR⁺ pts had a shorter time to CRPC than HRR⁰ pts (13.7 vs 31.3 months; HR: 2.2; p=0.001). 28 HRR⁺ pts (19 BRCA2, 8 ATM, 1 BRCA1) received olaparib, demonstrating a trend towards improved OS from mCRPC compared to HRR⁺ pts without PARPi (38.1 vs 17.4 mo, p=0.20). In 9 HRR⁺ pts without PARPi, 7 had androgen receptor pathway inhibitor (ARPi) tx and taxane, 1 had ARPi, and 1 had docetaxel. 50% of pts received olaparib after ≥2 systemic tx lines. A longer OS trend was observed in pts receiving 1st line mCRPC olaparib tx than pts receiving olaparib in later tx lines (17.2 vs 11.1 mo, p=0.07). OS from mCRPC was similar in HRR⁰ and olaparib tx HRR⁺ pts (37.4 vs 38.1 mo, p=0.70). In olaparib tx pts, median OS post initiation was 11.7 mo, rPFS was 5.4 mo, 36% had ≥50% PSA decline, and 29% had ≥30 days tx beyond PSA progression (PCWG3 criteria). SAE occurred in 39%; 4 pts required transfusion for anemia. Of 8 pts receiving additional systemic tx, 6 had taxane- and 2 had platinum-based chemotherapy.

Conclusions

In this study of heavily pre-treated mPCa pts, RW rPFS and OS on olaparib were reduced compared to clinical trials. Similar OS was seen in olaparib tx HRR⁺ and HRR⁰ pts, despite historically poorer prognosis in HRR⁺ pts. These results demonstrate that a biomarker driven tx approach and earlier access to PARPi may improve outcomes in HRR⁺ pts.

Clinical trial identification

Editorial acknowledgement

This was an ESCR performed with AstraZeneca funding support and collaboration.

Legal entity responsible for the study

The authors.

Funding

AstraZeneca.

Disclosure

S.M. Yip: Financial Interests, Personal, Advisory Board: Amgen, BMS, Novartis, Pfizer, Hoffman-La Roche, Ipsen; Financial Interests, Personal, Research Funding, Includes ad board/consultancy: Astellas, AstraZeneca, Merck, Bayer, Janssen; Financial Interests, Personal, Other, consultancy: Oncohelix. M. Kolinsky: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Merck, Janssen; Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, BMS, Eisai, Ipsen, Merck, Janssen; Financial Interests, Institutional, Research Grant: Janssen, AstraZeneca. T. Tucker: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Pfizer; Financial Interests, Institutional, Research Grant: Pfizer. P. Bose: Financial Interests, Personal, Ownership Interest, I am a co-founder and director in OncoHelix Inc: Oncohelix. T.A. Bismar: Financial Interests, Personal, Other, advisory role: xpherabio; Financial Interests, Institutional, Funding, funding support for fellow: AstraZeneca. D.Y.C. Heng: Financial Interests, Personal, Advisory Board: Pfizer, Merck, BMS, Ipsen, Novartis, AstraZeneca, Roche; Financial Interests, Personal, Steering Committee Member: Exilexis; Financial Interests, Institutional, Local PI: BMS, Pfizer, Ipsen. S. North: Financial Interests, Personal, Advisory Board, honoraria: Astellas, BMS, Janssen, Merck, Roche, Sanofi, Bayer, AstraZeneca; Financial Interests, Institutional, Local PI, per case funding: Sanofi, AstraZeneca, Ipsen, Astellas. N. Alimohamed: Financial Interests, Personal, Advisory Board: Bayer, Seagen, EMD Serono, BMS, Gilead. N.S. Basappa: Financial Interests, Personal, Advisory Board: Ipsen, Eisai, Pfizer, AstraZeneca, Janssen Inc, EMD Serono, Astellas, Bayer, BMS, Seagen, Takeda; Financial Interests, Institutional, Research Grant, Research Grant: Ipsen; Other, Other, Travel grant/support: Ipsen; Other, Other, Travel Grant/support: Eisai. K.N.N. Chi: Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, Janssen, Point Biopharma, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, BMS; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, Janssen, Novartis, Roche; Financial Interests, Institutional, Trial Chair: AstraZeneca, Arvinas, Janssen, Novartis; Financial Interests, Institutional, Local PI: Arvinas. S.E. El Hallani: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Full or part-time Employment: Alberta Precision Labs; Financial Interests, Institutional, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.