Activity of platinum-based chemotherapy in patients with advanced prostate cancer with and without DNA repair gene aberrations Journal Article
| Authors: | Schmid, S.; Omlin, A.; Higano, C.; Sweeney, C.; Martinez Chanza, N.; Mehra, N.; Kuppen, M. C. P.; Beltran, H.; Condeduca, V.; Vargas Pivato de Almeida, D.; Cotait Maluf, F.; Oh, W. K.; Tsao, C. K.; Sartor, O.; Ledet, E.; Di Lorenzo, G.; Yip, S. M.; Chi, K. N.; Bianchini, D.; De Giorgi, U.; Hansen, A. R.; Beer, T. M.; Lavaud, P.; Morales-Barrera, R.; Tucci, M.; Castro, E.; Karalis, K.; Bergman, A. M.; Le, M. L.; Zürrer-Härdi, U.; Pezaro, C.; Suzuki, H.; Zivi, A.; Klingbiel, D.; Schär, S.; Gillessen, S. |
| Article Title: | Activity of platinum-based chemotherapy in patients with advanced prostate cancer with and without DNA repair gene aberrations |
| Abstract: | Importance: 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. Objective: 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. Exposure: 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. Results: 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. |
| Journal Title: | JAMA Network Open |
| Volume: | 3 |
| Issue: | 10 |
| ISSN: | 2574-3805 |
| Publisher: | American Medical Association |
| Date Published: | 2020-10-01 |
| Start Page: | e2021692 |
| Language: | English |
| DOI: | 10.1001/jamanetworkopen.2020.21692 |
| PUBMED: | 33112397 |
| PROVIDER: | scopus |
| PMCID: | PMC7593810 |
| DOI/URL: | |
| Notes: | Erratum issued, see DOI: 10.1001/jamanetworkopen.2020.29176 -- Article -- Export Date: 1 December 2020 -- Source: Scopus |
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