Association of Rash With Outcomes in a Randomized Phase II Trial Evaluating Cetuximab in Combination With Mitoxantrone Plus Prednisone After Docetaxel for Metastatic Castration-resistant Prostate Cancer

This randomized phase II clinical trial analyzed the efficacy of combining cetuximab with mitoxantrone plus prednisone in men with progressive metastatic castrate-resistant prostate cancer after receiving docetaxel. Although the time to progression and overall survival did not improve with the addition of cetuximab, a hypothesis-generating analysis strongly suggests that men receiving cetuximab and developing a rash may benefit clinically. Purpose: Cetuximab (C), a chimeric monoclonal antibody that binds epidermal growth factor receptor (EGFR), is active against androgen-independent prostate cancer cell lines and might enhance the activity of chemotherapy. The efficacy of combining cetuximab with mitoxantrone (M) plus prednisone (MP) was evaluated in progressive metastatic castrate-resistant prostate cancer (CRPC) after receiving docetaxel. Materials and Methods: Patients with progression after receiving docetaxel were eligible and randomized 2:1 to CMP or MP. Therapy was mitoxantrone 12 mg/m(2) intravenously (I.V.) on day 1, oral prednisone 10 mg daily in both arms, and cetuximab 250 mg/m2 I.V. (400 mg/m2 day 1, cycle 1) on days 1, 8, and 15 in the CMP arm. Cycles were repeated every 21 days. Radiologic assessments of disease and PSA (prostate-specific antigen) occurred every 4 cycles. The primary endpoint was time to progression (TIP). Results: A total of 115 patients were enrolled, 75 in the CMP and 40 in the MP arm: the median TIP was 4.9 and 6.6 months, respectively; the measurable disease response rate was 2% and 4%, the PSA response rate 7.7% and 17.6%, and median survival 11.9 and 15.7 months, respectively. Key grade 3-4 toxicities were neutropenia 44% and 25.6%, anemia 6.7% and 7.7%, thrombocytopenia 6.7% and 2.6%, and fatigue 8% in both arms. In an unplanned exploratory analysis, median TIP with (n = 24) and without rash (n = 51) in the CMP arm was 10.3 months vs. 2.8 months (P = .004). On multivariable analysis, rash was significantly associated with TIP (hazard ratio [HR] = 0.43; P = .01). Conclusions: The treatment with CMP is not recommended in unselected men with docetaxel-treated CRPC, although rash might help develop tailored therapy. (C) 2012 Elsevier Inc. All rights reserved.