McWilliams RR, et al. - A randomized phase 2 study was undertaken to establish efficacy and to determine whether adding everolimus would increase the activity of the combination of carboplatin, paclitaxel, and bevacizumab (CPB). In this study, both the CPB and CPB with everolimus (CPBE) treatment arms demonstrated activity, with a progression-free survival of >5 months. The everolimus addition to CPB, however, failed to improve outcomes, with increased toxicity noted. These findings supported the moderate antitumor activity of CPB, with future development possibly in combination with targeted or immunotherapy.

Methods

• From May 2010 to May 2014, through the North Central Cancer Treatment Group, researchers randomized a total of 149 patients with unresectable AJCC 6th edition stage IV melanoma to either CPB or CPB with everolimus (CPBE).
• Progression-free survival (PFS) was observed as the primary end point.
• Secondary endpoints included overall survival (OS), response rate, and tolerability.

Results

• Regarding age (median age: 59 years vs 58 years) and high lactate dehydrogenase (48% vs 51%), the CPB and CPBE treatment arms were similar, but regarding sex (male sex: 72% vs 55%; P = .03), the two arms differed.
• Overall, no difference was observed regarding PFS, with a median PFS of 5.6 months for CPB versus 5.1 months for CPBE (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.81-1.62 [P = .44]), or OS, with a median OS of 14.5 months for CPB versus 10.8 months for CPBE (HR, 1.16; 95% CI, 0.84-1.84).
• For CPB, the confirmed response rate was 13% and for CPBE it was 23% (P = .13).
• For CPBE, toxicity was higher compared with CPB (83% for grade 3 + and 14% for grade 4 + vs 63% for grade 3 + and 11% for grade 4+, respectively) (toxicities were graded using the Cancer Therapy Evaluation Program of the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]).
• In this study, common grade 3 + toxicities included neutropenia, leukopenia, and fatigue, which occurred in both treatment arms with comparable frequency.