Safety and effectiveness of regorafenib (REG) in patients with metastatic colorectal cancer (mCRC) in routine clinical practice: An interim analysis (IA) from the prospective, observational CORRELATE study.

Abstract

700 Background: REG significantly improved overall survival (OS) vs placebo in patients with mCRC who progressed on available treatments in the randomized, double-blind, phase 3 trials CORRECT and CONCUR. CORRELATE aims to characterize the safety and effectiveness of REG for the treatment of mCRC in an unselected real-world patient population treated in routine clinical practice. Here we report the results of a planned IA. Methods: This global study aims to recruit 1000 patients with mCRC previously treated with approved therapies and for whom the decision to treat with REG has been made by the treating physician according to the local health authority approved label. Dose interruptions and reductions are permitted for the management of adverse events (AEs). The primary endpoint is the incidence of treatment-emergent AEs (TEAE; NCI-CTCAE v4.03). Secondary endpoints include OS, progression-free survival, and the disease control rate. The first planned interim analysis includes the first 500 patients observed for at least 3 months. Here, we report an IA of safety. Results: Median age was 65 years (range: 29–89) and 61% of patients were male. Most patients had a baseline ECOG PS 0/1 vs 2–4 (41%/43% vs 8%) and 50% had KRAS mutations. Most common metastatic sites at study entry were liver (52%) and lung (43%). The median treatment duration was 2.4 months (range: 0.1–10.6). The daily starting REG dose was 160 mg, 120 mg, and 80 mg in 53%, 34%, and 12% of patients, respectively; 26% of patients had dose reductions, 21% due to TEAEs. TEAEs of any grade occurred in 91% of patients, and in 76% TEAEs were considered REG related. Grade ≥ 3 TEAEs occurred in 55% of patients. In 31%, grade ≥ 3 TEAEs were REG related, with fatigue (7%), hand-foot skin reaction (5%), and hypertension (5%) being most common. Grade 5 TEAEs occurred in 13% of patients and were REG related in < 1%. Conclusions: In this observational study, the planned IA showed that the rate of REG-related grade ≥ 3 TEAEs appeared to be somewhat lower than rates observed in the phase 3 trials in patients with mCRC. The starting dose for approximately half the patients was less than 160 mg/day. Clinical trial information: NCT02042144.