Abstract 631P
Background
Immune checkpoint inhibitors have been approved for various solid tumors. However, their use in castration-resistant prostate cancer (CRPC) is still at an early phase of development.
Methods
Safety and efficacy of PD-L1 inhibitor avelumab plus carboplatin was investigated in a single-arm phase Ib study in patients with metastatic CRPC progressing to at least 1 taxane and 1 androgen receptor inhibitor. Patients received 2 cycles of carboplatin AUC5 followed by 2 cycles of avelumab 10mg/kg plus carboplatin AUC5, and by maintenance avelumab for 2 years. Safety was the primary endpoint. Secondary endpoints included PSA and radiographic responses, progression-free survival (PFS) and overall survival (OS). Germline and somatic mutation analysis was performed in all patients.
Results
26 patients were included. Median age was 70 years (range 55-83), 38.5% patients had visceral metastasis, 42.3% were ECOG PS0 and 57.7% PS1. Patients were heavily pretreated: 76.9% received ≥3 and 42.3% ≥4 treatment lines. Median treatment duration was 8.8 months (range 1.4-20.9) and median follow-up 14.2 months (95% CI 12.7-17.9). Safety profile was acceptable with 80% of patients experiencing AEs of any grade, 69% G3-4 AEs. Most frequent G3-4 AEs were: anemia (15/26, 57.7%) and thrombocytopenia (10/26, 38.4%). Confirmed PSA response rates ≥30% and ≥50% were seen in 15.4% (4/26) and 7.7% (2/26), respectively. Any reduction of PSA was seen in 34.6% of patients. Objective partial response rate in patients with measurable disease was 12.5% (2/16). These 2 responders had both a known HRD deleterious mutation (one BRCA2, one ATM). Disease control rate was 69.2% (18/26). Median radiographic PFS was 6.78 months (95% CI 4.28-9.01) and median OS 10.56 months (95% CI 6.68-NR). At the time of reporting these results, the overall genomic analysis is ongoing.
Conclusions
Avelumab plus carboplatin has an acceptable safety profile. Overall clinical benefit was seen in almost 70% of patients and was associated with a prolonged OS given the heavily pretreated population. A deleterious mutation in an HRD gene was present in the two patients showing a partial radiographic response.
Clinical trial identification
EudraCT 2017-004552-39.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This research was financially supported by Pfizer, as part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany.
Disclosure
A. Rodriguez-Vida: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: msd; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Takeda. J.P. Maroto Rey: Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: EUSA; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: BMS. A. Font Pous: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Pierre Fabre; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca. C. Martin: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: Roche. B. Mellado: Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi. A. Corbera Lloret: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Janssen. M. Orrillo Sarmiento: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD. O. Reig Torras: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Pzifer. R. Querol Ninerola: Other, Personal, Other: Boheringer Ingelheim; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Merck. N. Juanpere: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca. O. Juan: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca. J. Bellmunt: Financial Interests, Personal, Invited Speaker: Genentech; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Oncogenex; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Sanofi. All other authors have declared no conflicts of interest.