Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study.

BACKGROUND

Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation.

METHODS

These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models.

RESULTS

Of 1052 patients, 63%, 81%, 54%, 27%, 5.7%, and 8.0% had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio = 0.68 [95% confidence interval: 0.53-0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40-1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33-1.44]; p = 0.32) and metachronous/low-volume (0.22 [0.09-0.55]; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease.

CONCLUSION

TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC.

CLINICAL TRIAL REGISTRATION

NCT02489318.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Dr. Axel Merseburger reports consulting and advisory role for Astellas, AstraZeneca, Bristol-Myers Squibb, EUSAPharm, Ipsen, Janssen, Merck Serono, MSD, Novartis, Teva, Pfizer, Roche and Takeda; lectures/speaker/honoraria for/from Astellas, AstraZeneca, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck Serono, MSD, Novartis, Pfizer, Roche, Takeda and Teva; research and clinical studies for Astellas, AstraZeneca, Bristol-Myers Squibb, EUSAPharm, Ipsen, Janssen, Merck Serono, MSD, Novartis, Pfizer, Roche, Takeda and Teva. Dr. Neeraj Agarwal reports consulting and advisory role for Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics and Seattle Genetics; and research funding to institution from Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda and Tracon. Dr. Laurence Karsh reports consulting or advisory role for 3D Biopsy, Astellas, AstraZeneca, Bayer, Dendreon, Ferring, Janssen, Pfizer and Vaxiion; speakers’ bureau for Astellas, Bayer, Janssen, Pfizer and Clovis; honoraria from Astellas, Bayer, Janssen, Pfizer and Dendreon; stock or other ownership from Swan Valley Medical; research funding from Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Meyers Squibb, BU Optics, CUSP, Dendreon, Epizyme, Exact Sciences, Ferring, FKD, Genetech/Roche, GenomeDX, Genomic Health, Janssen, Merck, Myovant, Nucleix, OncoCell MDx, Pfizer, Pharmtech/Very, Precision Med and QED; and travel, accommodations and expenses from Astellas, Bayer, Dendreon, Janssen and Pfizer. Dr. Andrea Juliana Pereira de Santana Gomes reports consulting and advisory role for Janssen Oncology; speakers’ bureau for Astellas Pharma, Bayer and Janssen Oncology; research funding from Bayer, Janssen Oncology, MSD Oncology and Roche. Dr. Alvaro Juarez Soto reports consulting and advisory role for Astellas, Bayer and Janssen; meeting participation/lecturer for Astellas, Bayer and Janssen; investigator for Bayer and Janssen; meeting participation/lecturer for Astellas, Bayer and Janssen; clinical study participation for Janssen. Dr. Robert Given reports speakers’ bureau for Bayer, Janssen and Myovant; clinical study participation for Bayer and Janssen. Dr. Hirotsugu Uemura reports consulting and advisory role for AstraZeneca, Bayer, Janssen, MSD, Ono/BMS and Sanofi; meeting participation/lecturer for Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, Ono/BMS, Pfizer and Takeda; investigator for Astellas, AstraZeneca, Bayer, Janssen, MSD, Ono/BMS, Pfizer, Sanofi, Taiho and Takeda; clinical study participation for Bayer, Janssen, MSD and Ono/BMS. Dr. Simon Chowdhury reports consulting and advisory role to Astellas Pharma, Bayer, Beigene, Clovis, Janssen-Cilag, Johnson & Johnson, Novartis and Sanofi; research funding (self) from Clovis; and honoraria from Astellas Pharma, Bayer, Beigene, Clovis, Janssen-Cilag, Johnson & Johnson, Novartis and Sanofi. Dr. Kim Chi reports consulting and advisory role to Janssen, Astellas, Essa, Sanofi, Bayer, Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Merck, Bristol Myers Squibb and Point Pharma; research funding to institution from Janssen, Astellas and Sanofi; and honoraria from Janssen, Astellas, Bayer, AstraZeneca, Merck and Pfizer. Dr. Anders Bjartell reports consulting and advisory role for Astellas and Bayer; board membership/officer/trustee for Glactone Pharma and LIDDS Pharma; meeting participation/lecturer for Astellas, AstraZeneca, Bayer, Incyte, Ipsen, Janssen and Merk; clinical study participation for Astellas, Ferring and Janssen; stock ownership in Glactone Pharma, LIDDS Pharma and WntResearch. Dr. Amitabha Bhaumik, Dr. Florence Lefresne, Dr. Sabine Brookman-May, Dr. Suneel Mundle and Ms. Sharon McCarthy are employees of Janssen Research & Development and may hold stock in Johnson & Johnson. Dr. Amitabha Bhaumik also reports stock ownership of AbbVie.