1793P - PPROSTRATEGY: A SOGUG randomized trial of androgen deprivation therapy (ADT) plus docetaxel (dct) +/- nivolumab (nivo) or ipilimumab-nivolumab (ipi-nivo) in high-volume metastatic hormone-sensitive prostate cancer (hvHSPCa) - Safety and toxicity profiles from the pilot phase

Background

ADT+ dct has been a standard of care first-line for hvHSPC patients (pt). We hypothesized that early addition of ipi and/or nivo could improve outcomes.

Methods

PROSTRATEGY was designed as a seamless randomized (2/1/1) multi-arm multi-stage trial, to compare ADT+dct (75 mg/m² x6 cycles) vs ADT+dct→nivo (3 mg/Kg/2w x 12 mo), or ADT+ipi+dct→nivo (ADT + ipi 1 mg/Kg/3w x 2 cycles → dct x3 cycles → ipi 3mg/Kg/3w x2 cycles → dct x3 cycles → nivo x 12 mo) in hvHSPCa pt in 30 academic centers in Spain. The aims of the pilot phase were to check feasibility and safety (presented in this abstract) as well as to estimate efficacy outcomes. Dose reductions were only planned for dct. Primary prophylaxis with GCSF during dct was recommended, and secondary prophylaxis was mandatory.

Results

150 pt were randomized to dct (75 pt), dct-nivo (37 pt) or dct+ipi-nivo (38 pt). Mean age was 66.4 y (39% >70 y), 98% were Caucasian, 99.3% had ECOG 0-1, 88% were metastatic at diagnosis, mean PSA was 157 ng/ml, 88% had Gleason ≥ 8, 31% visceral involvement, and 17% received local therapy to the prostate, with no differences among arms. With a median follow-up of 32.5 mo from ADT, 60% of pt have progressed and 41.3% have died. Efficacy is described separately. Main adverse events (AEs) are summarized in the table. Two pt in the Dx+Ipi-Nivo arm died due to toxicity (1 pt febrile neutropenia and sepsis, 1 pt immune-related encephalitis).

Table: 1793P

Conclusions

The addition of ipi and/or nivo to ADT + Dct in pt with hvHSPCa is feasible. No unexpected or more frequent toxicities were observed in this trial with the addition of checkpoint inhibitors to ADT+ Dx. As expected, the addition of ipi + nivo to ADT+dct is associated with a slightly increase of immune-related AEs.

Clinical trial identification

EudraCT 2017-004377-13.

Editorial acknowledgement

Legal entity responsible for the study

SOGUG (Spanish Genitourinary Oncologic Group).

Funding

BMS.

Disclosure

J.A. Arranz Arija: Financial Interests, Personal, Advisory Board: Astellas, BMS, Merck, Pfizer, Bayer, MSD, Eisai; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Institutional, Coordinating PI, SOGUG: BMS. T. Alonso Gordoa: Financial Interests, Personal, Advisory Board: Ipsen, Pfizer, Roche, Sanofi, Bayer, Eisai, Novartis Advanced Accelerator Applications, Lilly, BMS, Astellas; Financial Interests, Personal, Invited Speaker: Janssen Cilag; Non-Financial Interests, Project Lead: Pfizer, Ipsen. B. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, BMS, Ipsen, EUSA Pharma, Merck, MSD, AstraZeneca, AAA; Financial Interests, Personal, Invited Speaker: BMS, Roche, Bayer, EUSA Pharma, MSD, Merck, Pfizer, Janssen, Astellas Pharma, AAA. M.A. Climent Duran: Financial Interests, Personal, Advisory Board: Roche, BMS, EUSA, Pfizer, Sanofi, Janssen, Astellas, Merck, Ipsen, MSD; Financial Interests, Personal, Invited Speaker: EUSA, Pfizer, Sanofi, Janssen, Astellas, merck, Ipsen, BMS, Roche, MSD. E. Gallardo Diaz: Financial Interests, Personal, Advisory Board: Sanofi, Janssen, Astellas, Pfizer, Bayer, Roche, Ipsen, Eisai, EUSA Pharma, BMS, AstraZeneca, Merck, Merck, Daiichi Sankyo, Techdow, Novartis, Lilly, Pfizer, Advanced Accelerator Applications, GSK; Financial Interests, Personal, Invited Speaker: Sanofi, Janssen, Astellas, Pfizer, Bayer, Roche, Ipsen, Eisai, EUSA Pharma, BMS, Merck, Daiichi Sankyo, MSD, Menarini, Rovi, Leo Pharma, Boehringer Ingelheim, Advanced Accelerator Applications; Financial Interests, Institutional, Local PI: Astellas, Medivation, Ipsen, Janssen, Pfizer, Lilly, Pfizer-Merck, MSD, BMS, Bayer, Daiichi Sankyo, Roche, AstraZeneca, Novartis, Seattle Genetics, Incyte, Aveo, Exelixis, Immunicum, Mediolanum, Clovis, QED Therapeutics; Non-Financial Interests, Leadership Role, Member of the Board: SOGUG; Non-Financial Interests, Leadership Role, Member of the Board of Thrombosis and Cancer Section: SEOM. M. Lázaro Quintela: Financial Interests, Personal, Invited Speaker: Roche, Eisai, Merck, Ipsen, Astellas, Novartis, Sanofi, Lilly; Financial Interests, Personal, Advisory Board: Astellas, Takeda, Pfizer, Ipsen. N. Lainez Milagro: Financial Interests, Personal, Advisory Board: Merck, Pfizer, Eisai, Ipsen; Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Ipsen, AstraZeneca, MSD. M.A. Gonzalez del Alba Baamonde: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, MSD, Bayer, BMS, EUSA PHARMA, Eisai, AAA, Roche; Financial Interests, Personal, Invited Speaker: Astellas, Merck; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Member of Board of Directors: SOGUG, SEOM. G. Crespo Herrero: Financial Interests, Personal, Advisory Board: BMS, AAA, Ipsen, Janssen, Sanofi, EUSA PHARMA, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche, Ipsen, Pierre Fabre, Janssen, Eisai, MSD, Novartis, Bayer, EUSA PHARMA. C. Alvarez Fernandez: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck-Pfizer; Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Ipsen, AstraZeneca. B. Mellado Gonzalez: Financial Interests, Personal, Other, Research Grant/Funding (Self), Speaker Bureau, Travel accommodation: Janssen, Roche, Astellas, Sanofi, Bayer; Financial Interests, Personal, Other, Speaker Bureau, Travel accommodation: Pfizer; Financial Interests, Personal, Other, Travel accommodation, Speaker Bureau: Ipsen; Financial Interests, Personal, Other, Speaker Bureau: BMS. F.J. Zambrana Tevar: Financial Interests, Personal, Invited Speaker: BMS, Ipsen. J.C. Villa Guzmán: Financial Interests, Personal, Invited Speaker: BMS, Merck, MSD, Pfizer. J.M. Piulats Rodriguez: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Roche, BMS, MSD, BeiGene, VCN, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS, Pfizer, Janssen, BeiGene, Mirati. All other authors have declared no conflicts of interest.