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)

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. Descriptive statistics are reported.

Results

Compared to the short PFS group, the long PFS group had a higher proportion of patients with ECOG PS 0, with no liver metastases, and ≥18 m since diagnosis of metastatic disease (Table). Long PFS patients 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 were 136 mg, 149 mg, respectively. 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%).