Activity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations
Wissenschaftlicher Artikel/Review - 01.10.2020
Schmid Sabine, De Giorgi Ugo, Hansen Aaron R, Beer Tomasz M, Lavaud Pernelle, Morales-Barrera Rafael, Tucci Marcello, Castro Elena, Karalis Kostas, Bergman Andries M, Le Mo Linh, Zürrer-Härdi Ursina, Pezaro Carmel, Suzuki Hiroyoshi, Zivi Andrea, Klingbiel Dirk, Schär Sämi, Bianchini Diletta, Chi Kim N, Omlin Aurelius, Higano Celestia, Sweeney Christopher, Martinez Chanza Nieves, Mehra Niven, Kuppen Malou C P, Beltran Himisha, Conteduca Vincenza, Vargas Pivato de Almeida Daniel, Cotait Maluf Fernando, Oh William K, Tsao Che-Kai, Sartor Oliver, Ledet Elisa, Di Lorenzo Giuseppe, Yip Steven M, Gillessen Silke
DNA repair gene aberrations occur in 20% to 30% of patients with castration-resistant prostate cancer (CRPC), and some of these aberrations have been associated with sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition platinum-based treatments. However, previous trials assessing platinum-based treatments in patients with CRPC have mostly included a biomarker-unselected population; therefore, efficacy in these patients is unknown.
To characterize the antitumor activity of platinum-based therapies in men with CRPC with or without DNA repair gene alterations.
Design, Setting, and Participants
In this case series, data from 508 patients with CRPC treated with platinum-based therapy were collected from 25 academic centers from 12 countries worldwide. Patients were grouped by status of DNA repair gene aberrations (ie, cohort 1, present; cohort 2, not detected; and cohort 3, not tested). Data were collected from January 1986 to December 2018. Data analysis was performed in 2019, with data closure in April 2019.
Treatment with platinum-based compounds either as monotherapy or combination therapy.
Main Outcomes and Measures
The primary end points were as follows: (1) antitumor activity of platinum-based therapy, defined as a decrease in prostate-specific antigen (PSA) level of at least 50% and/or radiological soft tissue response in patients with measurable disease and (2) the association of response with the presence or absence of DNA repair gene aberrations.
A total of 508 men with a median (range) age of 61 (27-88) years were included in this analysis. DNA repair gene aberrations were present in 80 patients (14.7%; cohort 1), absent in 98 (19.3%; cohort 2), and not tested in 330 (65.0%; cohort 3). Of 408 patients who received platinum-based combination therapy, 338 patients (82.8%) received docetaxel, paclitaxel, or etoposide, and 70 (17.2%) received platinum-based combination treatment with another partner. A PSA level decrease of at least 50% was seen in 33 patients (47.1%) in cohort 1 and 26 (36.1%) in cohort 2 (P = .20). In evaluable patients, soft tissue responses were documented in 28 of 58 patients (48.3%) in cohort 1 and 21 of 67 (31.3%) in cohort 2 (P = .07). In the subgroup of 44 patients with BRCA2 gene alterations, PSA level decreases of at least 50% were documented in 23 patients (63.9%) and soft tissue responses in 17 of 34 patients (50.0%) with evaluable disease. In cohort 3, PSA level decreases of at least 50% and soft tissue responses were documented in 81 of 284 patients (28.5%) and 38 of 185 patients (20.5%) with evaluable disease, respectively.
Conclusions and Relevance
In this study, platinum-based treatment was associated with relevant antitumor activity in a biomarker-positive population of patients with advanced prostate cancer with DNA repair gene aberrations. The findings of this study suggest that platinum-based treatment may be considered an option for these patients.