Abstract 1793P
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
Dct | Dct → Nivo | Dct +Ipi → Nivo | |
Any AE Any serious AE | 97.3% 18.7% | 97.3% 62.2% | 100% 39.5% |
Treatment-related G3-4 AEs Any Infusional reactions Anemia Neutropenia Febrile neutropenia Thrombocytopenia ALT/AST Diarrhea/colitis Mucositis Rash/dermatitis Arthomialgias Peripheral neuropathy Myasthenic sd Hypophysitis Myocarditis Nephritis Encephalitis | 34.7% 0% 0% 4.0% 6.7% 0% 0% 1.3% 0% 0% 0% 2.7% 0% 0% 0% 0% 0% | 67.6% 0% 2.7% 8.1% 5.4% 0% 2.7% 5.4% 2.7% 0% 0% 0% 2.7% 0% 0% 0% 0% | 60.5% 2.6% 2.6% 2.6% 2.6% 0% 2.6% 5.3% 0% 2.6% 2.6% 0% 0% 2.6% 2.6% 2.6% 2.6% |
Dct dose reduction Discontinuation due to AEs docetaxel nivolumab ipilimumab | 22.7% 2.6% - - | 27% 2.7% 5.4% - | 7.9% 7.9% 5.4% 2.7% |
Treatment-related dead | 0% | 0% | 5.4% |
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.
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