Phase 2 Trial Evaluates NEXIRI Regimen for Heavily Pretreated KRAS Mutation-positive mCRC

Sorafenib plus irinotecan (NEXIRI) is efficacious for the treatment of patients with refractory KRAS mutation-positive metastatic colorectal cancer (mCRC), a study presented at the 2016 Gastrointestinal Cancers Symposium in San Francisco, CA, has shown.¹

Because the NEXIRI regimen demonstrated promising activity with a disease control rate of 65% in heavily pretreated patients with mutated KRAS mCRC in a phase 1/2 study, researchers sought to determine the 2-month progression-free survival rate of NEXIRI compared with irinotecan or sorafenib monotherapy in this patient population.

For the study, researchers enrolled 173 patients with progressive measurable and non-resectable mutant KRAS mCRC with an ECOG performance status of 0 or 1 who were refractory to irinotecan, oxaliplatin, fluoropyrimidines, and bevacizumab.

Participants were randomly assigned 1:1:1 to receive irinotecan 120 – 180 mg/m² biweekly plus sorafenib 400 mg orally twice daily, irinotecan 180 mg/m² alone, or sorafenib alone until disease progression or unacceptable toxicity. Patients in the monotherapy arms were eligible to crossover to NEXIRI at progression.

Results showed that the 2-year progression-free survival rate was 59% (95% CI, 39 – 66) with NEXIRI, 23% (95% CI, 10 – 33) with irinotecan, and 22% (95% CI, 8 – 30). The disease control rate was 59%, 25%, and 22%, respectively, with 4 patients in the NEXIRI arm achieving a partial response.

Researchers found that median progression-free survival was 3.7 months (95% CI, 2.2 – 4.9) in the combination group, 1.9 months (95% CI, 1.7 – 2.1) in the irinotecan arm, and 2.1 months (95% CI, 1.9 – 2.5) in the sorafenib alone group. Median overall survival was 7.0 months (95% CI, 5.8 – 9.4), 6.3 months (95% CI, 4.8 – 8), and 5.1 months (95% CI, 3.7 – 7.7), respectively.

In terms of toxicity, grade 3 or 4 neutropenia occurred in 18% of NEXIRI patients compared with 6% of irinotecan patients and none in the sorafenib arm. A total of 26% of patients in the NEXIRI arm reported grade 3 or 4 diarrhea vs 7% each in both of the monotherapy arms. The rate of grade 3 or 4  hand-foot syndrome was similar in the NEXIRI and sorafenib arm (17% vs 16%, respectively).

“These results justify comparing this combination to regorafenib or [trifluridine/tipiracil] monotherapies in this population,” the authors concluded. “Ancillary studies are ongoing to identify biomarkers.”

Reference

1. Samalin E, De La Fouchardiere C, Thezanas S, et al. Sorafenib and irinotecan combination for pre-treated RAS-mutated metastatic colorectal cancer patients: A multicentre randomized phase II trial (NEXIRI 2) [abstract]. J Clin Oncol. 2016;34(suppl 4S; abstr 635).