Abstract 1799P
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.
Resources from the same session
1250P - Assessing lung carcinoma: A retrospective study on volume evaluation, consolidation and infiltration using chest OMX
Presenter: Swarnambiga Ayyachamy
Session: Poster session 14
1251P - Development of a deep learning algorithm for lung cancer diagnosis using methylation and fragment size profiles of cfDNA
Presenter: Jiyoung Huh
Session: Poster session 14
1252P - Quantitative cell signaling activity profiling of solid tumors to support personalized treatment in the FINPROVE basket trial: Presentation of skin tumor data
Presenter: Diederick Keizer
Session: Poster session 14
1253P - Analytic validation and implementation of OncoDEEP: A pan-cancer comprehensive genomic profiling NGS assay for assessing homologous recombination deficiency (HRD)
Presenter: Marcel Trautmann
Session: Poster session 14
1254P - Retrospective analysis of brain OMX: Diagnostic tool for structural (T1) and functional connectome (RS-FMRI) analysis of brain
Presenter: Swarnambiga Ayyachamy
Session: Poster session 14
1255P - Evaluating GPT-4 as an academic support tool for clinicians: A comparative analysis of case records from the literature
Presenter: Marcos Aurelio Fonseca Magalhaes Filho
Session: Poster session 14
1256P - Value of detection of peripheral blood circRNA based on digital PCR in the diagnosis of lung adenocarcinoma
Presenter: Jihong Zhou
Session: Poster session 14
1257P - Double heterozygous prevalence in hereditary cancer syndromes in Northern Mexico population
Presenter: Carlos Burciaga Flores
Session: Poster session 14
1258P - Does FDG PET-based radiomics have an added value for prediction of overall survival in non-small cell lung cancer?
Presenter: Andrea Ciarmiello
Session: Poster session 14
1260TiP - Enhancing lung nodule discrimination with a novel cfDNA test: The cancer signature ensemble (CSE) approach
Presenter: Young-Chul Kim
Session: Poster session 14