Cobimetinib (C) + paclitaxel (P) as first-line treatment in patients (pts) with advanced triple-negative breast cancer (TNBC): Updated results and biomarker data from the phase 2 COLET study.

1074 Background: C is a highly selective MEK inhibitor. Up-regulation of the MAPK pathway may confer resistance to taxane therapy. Because resistance to taxanes occurs in most TNBC pts and many TNBC tumors harbor genetic alterations in the MAPK pathway, the combination of C+P may be beneficial. Methods: COLET (NCT02322814) is evaluating the safety and efficacy of C+P in pts with metastatic/locally advanced TNBC and no prior systemic therapy for metastatic disease. There are 2 stages: a safety run-in (n≈12) followed by a 1:1 randomized stage (n≈100 pts) to C+P or placebo (PBO) + P. Pts receive P 80 mg/m2 on Days 1, 8, and 15 and C/PBO 60 mg/d on Days 3-23 of each 28-d cycle until disease progression or unacceptable toxicity. Safety stage is complete and the randomized stage is enrolling. Results: Between Mar 12, 2015, and Jun 8, 2015, 16 pts were enrolled in the safety stage. All were women (median age, 55 years). At data cutoff (Dec 1, 2015), 14 pts had completed ≥1 cycle; all 16 pts received ≥1 dose of study treatment and were included in the safety review. Median time on treatment was 135 d (range, 1-245). 94% of pts had ≥1 adverse event (AE). Most common (≥20%) AEs of any grade were diarrhea (63%), rash (50%), nausea (44%), alopecia (31%), and pyrexia, blood CPK level increase, asthenia, dyspnea, edema peripheral, stomatitis, vomiting, and constipation (all 25%). 9 pts (56%) had grade 3 AEs; there were no grade 4-5 AEs. Serous retinopathy is a known AE of C; in this study, 2 pts reported one grade 1 AE each. Preliminary efficacy from safety run-in included unconfirmed partial response (n = 8), stable disease (n = 3), and progressive disease (n = 3); 2 pts had not completed a tumor assessment. Mutation and copy number changes in oncogenes, tumor suppressors, and other genes associated with TNBC will be reported. Conclusions: This is the first study to evaluate C+P in TNBC. The safety profile of C+P is consistent with known safety profiles. Initial results are promising, and enrollment in the randomized stage is ongoing (primary efficacy outcome of progression-free survival). Pts in the safety stage continue to be followed up for long-term safety and disease progression. Clinical trial information: NCT02322814.