Platinum-Based Treatment Associated with Antitumor Activity in Some Patients with Advanced Prostate Cancer

A study published in JAMA Network Open found that 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.

Researchers suggested that these findings show that platinum-based treatment may be considered an option for this patient population. However, these results still require prospective validation.

“Based on our analysis, platinum-containing therapy should be considered in patients with DNA repair gene aberrations, especially if access to a PARP inhibitor is not available,” the authors wrote.

In this case series, researchers collected data on 508 patients with castration-resistant prostate cancer (CRPC) treated with platinum-based therapy from 25 academic centers from 12 countries worldwide. Patients were grouped by status of DNA repair gene aberrations, including those with aberrations present, not detected, and not tested.

The dual primary end points for the study were 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 the association of response with the presence or absence of DNA repair gene aberrations.

Of the 508 men included in the analysis, DNA repair gene aberrations were present in 80 patients (14.7%), absent in 98 (19.3%), and not tested in 330 (65.0%). Moreover, of 408 patients who received platinum-based combination therapy, 338 patients (82.8%) received docetaxel (Taxotere), paclitaxel (Abraxane), or etoposide (Etopophos), and 70 (17.2%) received platinum-based combination treatment with another partner.

“This series is unique because it is among the largest to date that evaluates patients with identified DNA repair gene aberrations who received a platinum-based chemotherapy, very few of whom had previously received treatment with a PARP inhibitor because use of these agents outside of clinical trials was very limited,” the authors noted.

A PSA level decrease of at least 50% was observed in 33 patients (47.1%) with aberrations present and in 26 (36.1%) with no aberrations detected (P = .20). Moreover, in evaluable patients, soft tissue responses were documented in 28 of 58 patients (48.3%) with aberrations present and 21 of 67 (31.3%) with no aberrations (P = .07). In those not tested for genomic aberrations, 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.

Notably, in a 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.

“Overall, different DNA repair gene aberrations are most likely distinct entities with varying responses to platinum as well as PARP inhibition; therefore, they cannot be collectively addressed,” the authors explained. “More research with prospective trials in molecular subgroups is needed to better characterize which patients might derive benefit.”

Importantly, the 330 patients who were not tested for genomic aberrations most likely represent a mixed population according to the researchers, including perhaps some patients with DNA repair gene aberrations, and therefore the results of this cohort should be interpreted with caution.

“Currently, several prospective phase 2 trials (randomized and nonrandomized) evaluating carboplatin (Paraplatin) alone or in combination with docetaxel in molecularly selected patients with CRPC are recruiting,” added the authors.

Reference:

Schmid S, Omlin A, Higano C, et al. Activity of Platinum-Based Chemotherapy in Patients With Advanced Prostate Cancer With and Without DNA Repair Gene Aberrations. JAMA Network Open. doi: 10.1001/jamanetworkopen.2020.21692