1630P - A multicenter retrospective study on the efficacy of anti-PD-(L)1 in microsatellite unstable (MSI-H) metastatic castrate-resistant prostate cancer (mCRPC)

Background

Up to 5% of patients (pts) with mCRPC harbor loss of function alterations in mismatch repair genes (MMRd) resulting in an MSI-H phenotype. While MSI-H tumors are susceptible to immune checkpoint blockade (ICB) irrespective of tumor type, data on the efficacy of ICB in MSI-H mCRPC are limited. We present the results of an international, multicenter, retrospective study on the efficacy of anti-PD-(L)1 monotherapy in MSI-H mCRPC.

Methods

Clinical data of MSI-H mCRPC pts treated with anti-PD-(L)1 monotherapy were retrospectively collected in 15 different hospitals. MSI-H could be detected through next-generation sequencing, polymerase chain reaction, immunohistochemistry and/or germline testing. Primary endpoint was progression-free survival (PFS). Secondary and exploratory endpoints included objective response rate (ORR) according to RECIST1.1, PSA50 and PSA90 responses, overall survival (OS) and associations between clinical outcome and baseline (BL) characteristics.

Results

Between July 2016 and December 2023, 71 pts with a median age of 70 years (range 46-87) initiated anti-PD-1 (94%) or anti-PD-L1 (6%) treatment. At BL, 21 pts (30%) had visceral metastases. Median tumor mutational burden was 39.8 mut/Mb (range 4-268). Thirty-two pts (45%) were treated with docetaxel and/or novel hormonal agents in the hormone-sensitive setting. Median number of prior therapies in the CRPC setting was 1 (0-8). Following anti-PD-(L)1 therapy, median PFS was 8.3 months (95% CI 5.5 – 17.5), with 1, 2 and 3-year PFS rates of 40.4%, 25.4%, and 22.9%. In RECIST1.1 evaluable pts (n=62), the ORR was 48%. PSA50 and PSA90 responses were observed in 60% and 46% of pts with available PSA data (n=52). Median OS was 30.1 months (95% CI 17.8 – NR). Associations between outcome and clinical and molecular characteristics will be presented.

Conclusions

Our data support the early utilization of anti-PD-(L)1 monotherapy in pts with MSI-H mCRPC, with similar responses and outcomes in MSI-H mCRPC compared to non-colorectal MSI-H.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A.M. Bergman: Financial Interests, Institutional, Advisory Board: Astellas, Jansen, Bayer, Sanofi; Financial Interests, Institutional, Research Grant: Amgen, Astellas, Bayer, Sanofi; Other, Financial support for attending conferences: Astellas, Sanofi, Bayer. A. Bernard-Tessier: Financial Interests, Personal, Invited Speaker: Astellas, Bayer, AstraZeneca; Financial Interests, Personal, Other, travel fees: ORION; Financial Interests, Institutional, Advisory Board: NOVARTIS, Roche, Janssen, MSD, AAA-Novartis; Financial Interests, Personal, Writing Engagement: Bouchara-Recordati; Non-Financial Interests, Principal Investigator: AMGEN, Macrogenics, Janssen. D. Robbrecht: Financial Interests, Institutional, Advisory Board: Merck AG, Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Astellas; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Coordinating PI: Treatmeds, DUOS; Financial Interests, Institutional, Coordinating PI, For study purposes: Merck AG; Non-Financial Interests, Advisory Role: Bayer; Non-Financial Interests, Principal Investigator: Sanofi, Incyte, Roche, InteRNA, Numab Therapeutics, Menarini. C.A. Rothermundt: Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, MSD Oncology, IPSEN; Financial Interests, Institutional, Expert Testimony: MSD Oncology. A.G. Omlin: Financial Interests, Institutional, Advisory Role: AbbVie, Accord, Advanced accelerator applications (AAA), Molecular Partners, Monrol, Myriad, Pfizer, Roche, Sanofi Aventis; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Astellas, Bayer, Janssen, Merck, MSD, Novartis; Financial Interests, Institutional, Speaker’s Bureau: Astellas, Bayer, Janssen; Financial Interests, Personal, Other, Travel support: Astellas, Bayer, Janssen, Sanofi Aventis. O. Sartor: Financial Interests, Institutional, Speaker, Consultant, Advisor: Advanced Accelerator Applications (AAA), Amgen, ARTbio, Astellas, AstraZeneca, Bayer, Clarity Pharmaceuticals, Fusion, ITM Oncologics, JNJ, Lantheus, Merck, Noria Therapeutics, Novartis, Pfizer, RATIO, Sanofi, Telix; Financial Interests, Personal, Other, Equity: ARTBio, Clarity, Fusion, JNJ, Lilly, Pfizer, RATIO; Financial Interests, Institutional, Research Funding: AAA, Amgen, AstraZeneca, Bayer, JNJ, Lantheus, Novartis, Telix. L. Sena: Financial Interests, Institutional, Research Funding: Panbela Therapeutics. H. Beltran: Financial Interests, Personal, Advisory Board: Pfizer, Janssen, Foundation Medicine, Blue Earth Diagnostics, AstraZeneca, Amgen, Diaachi Sankyo, Merck, LOXO, Sanofi, Curie Therapeutics, Fusion Pharma; Financial Interests, Institutional, Funding: Janssen, AbbVie/Stemcentrx, Bristol Myers Squibb,; Financial Interests, Institutional, Research Grant: Diaachi Sankyo, Circle Pharma; Financial Interests, Personal and Institutional, Steering Committee Member: Novartis. J.S. de Bono: Financial Interests, Personal, Advisory Board: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Menarini Silicon Biosystems, ImCheck Therapeutics, Crescendo, MetaCurUm, Myricx, Nurix Therapeutics, Oncternal Therapeutics; Financial Interests, Institutional, Advisory Board: Harpoon, Dark Blue Therapeutics, Novartis, Takeda, Tango Therapeutics; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Bayer, Cellcentric, Daiichi Sankyo, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Sanofi Aventis, Sierra Oncology, Taiho, Vertex Pharmaceuticals, Crescendo Biologics, Menarini Silicon Biosystems, Immunic Therapeutics, MetaCurUm, Myricx, Nurix Therapeutics, Oncternal Therapeutics; Financial Interests, Institutional, Local PI: Amgen; Non-Financial Interests, Principal Investigator: Amgen, Astellas, AstraZeneca, Bayer, Bioxcel Therapeutics, Boehringer Ingelheim, Cellcentric, Daiichi Sankyo, Eisai, Genentech Roche, Genmab, GSK, Harpoon, Janssen, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma, Pfizer, Qiagen, Sanofi Aventis, Sierra Oncology, Taiho, Terumo, Vertex Pharmaceuticals, Crescendo, ImCheck Therapeutics, Immunic Therapeutics; Non-Financial Interests, Institutional, Product Samples: Daiichi Sankyo, Bayer, Merck Serono, AstraZeneca, Harpoon, Pfizer, Sierra Oncology, Genentech/Roche, Sanofi Aventis, GSK. N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, MSD, Astrazeneca, Astellas, JNJ, Bayer; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Other, An predictive biomarker IP is being validated / no income / no royalties: EUROSTAR grant for predictive biomarker in urothelial cancer; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Coordinating PI: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: Astrazeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, co-PI / multi-dharma sponsored: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-resistant Prostate Cancer Registry; Non-Financial Interests, Principal Investigator, RWD registry de novo mHSPC: TripleAIM1 / Janssen. All other authors have declared no conflicts of interest.