D27 - Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the phase 3b CONSIGN trial who had progression-free survival (PFS) >4 months (m)

Abstract

Background: In the phase 3 randomized CORRECT trial, REG improved survival vs placebo in treatment-refractory mCRC; 19% of REG-treated patients had PFS >4 m. In the single-arm phase 3b CONSIGN trial (NCT01538680) of REG, adverse events (AEs) and PFS were consistent with phase 3 trials in mCRC. We performed a retrospective analysis of CONSIGN patients with PFS >4 m (long PFS) and ≤4 m (short PFS). Methods: Patients with treatment-refractory mCRC received REG 160 mg QD for 3 wks on/1 wk off until disease progression, death, or unacceptable toxicity. Treatment beyond progression was at the investigator's discretion. PFS (investigator assessed) was the time from treatment assignment to progression or death. Of 2872 patients assigned to REG, 674 (23%) had long PFS and 2198 (77%) had short PFS. Baseline characteristics, safety, and dosing parameters were analyzed descriptively. Results: The long PFS group had a higher proportion of ECOG 0 patients (Table) and received a median of 7 cycles (2–29); 75% ≥6 cycles; 34% ≥9 cycles. Short PFS patients received a median of 2 cycles (1–33). Dose reductions due to AEs (long PFS, short PFS) were 65%, 40%; actual mean daily doses 136 mg, 149 mg; and mean percent of planned dose 74%, 75%. The most common drug-related NCI-CTCAE v4 grade ≥3 AEs (long PFS, short PFS) were hypertension (20%, 14%), hand–foot skin reaction (19%, 12%), fatigue (13%, 13%), diarrhea (8%, 4%), and hypophosphatemia (8%, 4%). Conclusions: This exploratory analysis showed a similar proportion of patients in CONSIGN with PFS >4 m as in CORRECT. Higher proportions of long PFS patients had ECOG 0 and ≥18 m since diagnosis of metastatic disease. The higher AE and dose reduction rates in the long PFS group may be due to longer treatment duration.Table: D27Long PFS (n = 674)Short PFS (n = 2198)All (N = 2872)Median age, years (range)62 (27–86)62 (19–89)62 (19–89)ECOG PS, %05844471415653Primary site, %Colon666464Rectum282828Both688KRAS, %Mutant475251Wild-type494345No. of prior regimens on or after diagnosis of metastatic disease, %0-22228263282727≥4504546Time since first diagnosis of metastatic disease to treatment assignment, %<18 m92018≥18 m917982 Open table in a new tab