Single-agent PD-1/PD-L1 inhibitors have shown limited efficacy in unselected mCRPC. The evidence of a survival benefit with sipuleucel-T and ipilimumab, provides a rationale to study further increasing immunogenicity in mCRPC through combinations.
Safety and efficacy avelumab plus carboplatin was investigated in a single-arm Phase Ib study in mCRPC, progressing to at least one taxane and one androgen-receptor inhibitor. The primary endpoint was safety. Secondary endpoints included PSA/radiographic responses, progression-free survival (PFS) and overall survival (OS). Germline/somatic mutation analysis was performed.
In total, 26 patients were included. Patients were heavily pretreated: 76.9% received ≥3 and 42.3% ≥4 prior lines. A DNA damage repair (DDR) alteration was found in three patients (11.5%). The safety profile was acceptable with 73% Grade 3–4 treatment-related adverse events. PSA response rate ≥50% was seen in 7.7% of patients. The objective response rate was 17.6%, including one complete response (5.9%). Two of these responders had a known DDR alteration (one BRCA2, one ATM). The median response duration was 6 months. Median radiographic PFS was 6.6 months (95% CI 4.28–9.01), and median OS 10.6 months (95% CI 6.68–NR).
Avelumab plus carboplatin has an acceptable safety profile and was associated with a prolonged OS given the heavily pretreated population.
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The datasets generated and/or analysed during this study are available from the corresponding author upon reasonable request.
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Study was carried out by Pivotal CRO. Statistical analyses were performed by Tania San José. The Sponsor of the study was APRO (Associació per la recerca oncològica, Spanish Oncology Research Group).
Funding for this study was jointly provided through an unrestricted educational grant from Pfizer, Inc, New York, NY, USA and Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer. Pfizer and Merck reviewed the manuscript for medical accuracy only before journal submission. The authors are fully responsible for the content of this manuscript, and the views and opinions described in the publication reflect solely those of the authors.
Ethics approval and consent to participate
The study was carried out with the approval of the Institutional Ethics committee of all participating institutions. The study was conducted in accordance with the ethical principles pronounced in the Declaration of Helsinki (Amendment 64th of the World Medical Association General Assembly, Fortaleza, Brazil, October 2013). This study was registered at the European Union Drug Regulating Authorities Clinical Trials Database as EudraCT Number 2017-004552-39.
Consent to publish
A signed informed consent was obtained from each participant prior to any study procedure.
Dr. JB reports serving in an advisory role to Genentech, MSD, Pfizer, GSK, BMS, AstraZeneca, Pierre-Fabre, Sanofi Aventis, Astellas, OncoGenex, and Janssen; receiving honoraria or travel expenses from Pfizer, MSD, GSK, Novartis, Pierre-Fabre, Astellas, and BMS; and receiving research funding from Takeda, Pfizer, Novartis, and Sanofi Aventis. Dr. AR-V reports serving in an advisory role for MSD, Pfizer, BMS, Astellas, Janssen, Bayer, Clovis and Roche; receiving honoraria or travel expenses from Pfizer, MSD, Astellas, BMS, Janssen, AstraZeneca, Roche, Bayer, and Sanofi Aventis; and receiving research funding from Takeda, Pfizer, and Merck. Dr. PM reports serving in advisory board for Pfizer, Ipsen, and BMS. Dr. AF reports serving in an advisory role to Janssen, Astellas, Sanofi, Eusa; and receiving research funding from AstraZeneca. Dr. BM has received consulting fees from Pfizer, Roche, AstraZeneca, Bayer, Astellas Pharma, and Janssen, support for attending meetings or travel from Janssen-Cilag; and other financial or non-financial interests from Roche, Janssen, and Bayer. Dr. AT reports personal fees and non-financial support from Roche, BMS, MSD, GSK, AstraZeneca and Pfizer. Dr. AC reports receiving honoraria or travel expenses from Astellas, BMS, Janssen, and Merck. Dr. RQ repots Personal fees and non-financial support from Merck, Sanofi Aventis, Roche, Pfizer, Jansen, Amgen and Astellas. Dr. OJ declares being an employee of Pivotal SLU. Dr. MM-G reports serving in an advisory role for Roche, Seagen and Pierre-Fabre; receiving honoraria or travel expenses from Roche and Pfizer. Dr. NJ reports serving in an advisory role for AstraZeneca; and receiving honoraria or travel expenses from Roche and MSD. Dr. Oscar Reig, Dr. AR-H, Dr. MO and Dr. CM report no competing interests.
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Rodriguez-Vida, A., Maroto, P., Font, A. et al. Safety and efficacy of avelumab plus carboplatin in patients with metastatic castration-resistant prostate cancer in an open-label Phase Ib study. Br J Cancer 128, 21–29 (2023). https://doi.org/10.1038/s41416-022-01991-4