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.
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.
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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.”
- 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).