Adding Carboplatin to Cabazitaxel Improves PFS in Aggressive Variant CRPC

Adding carboplatin to cabazitaxel was safe and associated with improved PFS among men with aggressive variant castration-resistant prostate cancer.

Adding carboplatin to cabazitaxel was safe and associated with improved progression-free survival (PFS) among men with castration-resistant prostate cancer (CRPC), and particularly men with aggressive variant prostate carcinoma (AVPC), according to a randomized phase II trial presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 5020).

Molecular profiling suggested higher androgen receptor–negative and higher proliferation rates among study participants meeting AVPC clinical criteria, reported senior study author Ana M. Aparicio, MD, of the University of Texas MD Anderson Cancer Center in Houston, in a poster presentation.

The study authors hypothesized that carboplatin would benefit men with metastatic CRPC and men identified with AVPC using molecular criteria. A total of 160 men with metastatic CRPC were enrolled in the study between 2013 and 2015, and were randomly assigned 1:1 to receive cabazitaxel (25 mg/m2) with or without carboplatin (AUC, 4) every 21 days. The men were stratified based on clinically defined AVPC.

The researchers also sought to test a candidate molecular signature of AVPC (AVPC-m). They conducted immunohistochemical and gene-sequencing panels with tumor samples obtained from trial participants to determine concordance of the candidate AVPC-m signature with AVPC previously identified using clinical criteria. The candidate AVPC-m signature was defined as two or more alterations in p53, RB1, and/or PTEN.

At a median follow-up of 21.6 months, median PFS in the overall population was 7.4 months in the cabazitaxel + carboplatin group vs 4.59 months in the cabazitaxel-only group (P = .004). A subsequent subgroup analysis showed that carboplatin-associated improvement in median PFS remained statistically significant among men with clinically defined AVPC (5.64 months in the cabazitaxel + carboplatin group vs 3.75 months in the cabazitaxel-only group; P = .012), but not among men with non-AVPC metastatic CRPC (7.8 months vs 5.2 months; P = .09).

Common adverse events included fatigue, nausea, vomiting, dyspnea, and constipation. Three cases of grade 4 thrombocytopenia and seven cases of grade 4 neutropenia occurred in the cabazitaxel + carboplatin group, vs one and no such cases, respectively, in the cabazitaxel-only group.

“Additional analyses are ongoing to test the candidate AVPC-m signature in these samples, as well as the rate of alterations in other pathways (eg, DNA damage repair),” the authors wrote.

The researchers will next conduct a phase III study with overall survival as the primary endpoint.