A phase 3 trial failed to reveal the optimal sequence of treatment for patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC).
The trial’s primary endpoint was not met, and there were no significant differences in most efficacy outcomes between the treatment arms. However, there was a significant difference in response rates after induction.
These results, from the STRATEGIC-1 trial, were presented at the 2022 ASCO Annual Meeting.
The trial (ClinicalTrials.gov Identifier: NCT01910610) included 263 patients with previously untreated, unresectable mCRC who did not have mutations in KRAS, NRAS, or BRAF. The patients were randomly assigned to treatment arm A (n=131) or treatment arm B (n=132). Baseline characteristics were similar between the arms.
In arm A, patients received induction with cetuximab plus FOLFIRI (leucovorin, fluorouracil, and irinotecan) continuously until disease progression or unacceptable toxicity. Second-line therapy was continuous bevacizumab plus mFOLFOX6 (leucovorin, fluorouracil, and oxaliplatin), and 63% of patients in arm A proceeded to second-line therapy.
In arm B, patients received induction with bevacizumab plus OPTIMOX (stop-and-go oxaliplatin with continuous fluorouracil). Fifty-five percent of patients went on to second-line therapy, which was FOLFIRI-bevacizumab. Thirty-six percent of patients went on to third-line treatment, which was an anti-EGFR monoclonal antibody (cetuximab or panitumumab, with or without irinotecan).
The study’s primary endpoint was duration of disease control (DDC), which was defined as the sum of progression-free survival (PFS) of each active sequence of treatment.
There was no significant difference between the treatment arms for DDC, PFS after first-line therapy, or PFS after second-line therapy. The median DDC was 22.5 months in arm A and 23.5 months in arm B (hazard ratio [HR], 0.97; 95% CI, 0.72-1.29; P =.805).
The median PFS with induction was 11.7 months for arm A and 11.9 months for arm B (HR, 1.07; 95% CI, 0.82-1.39; P =.631). The median PFS with second-line treatment was 7.3 months in arm A and 6.2 months in arm B (HR, 1.01; 95% CI, 0.72-1.42; P =.945).
There was a trend toward an improvement in overall survival (OS) with arm A, but this was not statistically significant. The median OS was 37.8 months for arm A and 34.4 months for arm B (HR, 1.26; 95% CI, 0.94-1.70; P =.121).
Response rates differed between the treatment arms with induction but not with second-line treatment. Response rates with induction were 82.4% for arm A and 69.7% for arm B (P <.001). With second-line treatment, the response rates were 21.2% and 18.3%, respectively (P =.734).
The overall incidence of adverse events (AEs) was similar between the treatment arms — 99.2% in arm A and 97.7% in arm B. Rates of grade 3-4 AEs (72.7% and 72.0%, respectively) and serious AEs (46.9% vs 53.8%) were similar as well.
Disclosures: This research was supported by GERCOR in collaboration with Hoffmann-La Roche. Some study authors declared affiliations with or received grant support from the pharmaceutical industry. Please see the reference for a full list of disclosures.
Chibaudel B, Dourthe LM, Andre T, et al. STRATEGIC-1: Multi-line therapy trial in unresectable wild-type KRAS/NRAS/BRAF metastatic colorectal cancer—A GERCOR-PRODIGE randomized open-label phase III study. Presented at ASCO 2022; June 3-7, 2022. Abstract 3504.