STRATEGIC-1: multiple-line, randomized, open-label GERCOR-PRODIGE-39 phase III trial in unresectable RAS/BRAF wild-type metastatic colorectal cancer

Clinical Snapshot

Key Findings

• P Value: p = 0.945 (non-significant)

• Effect Size: HR = 1.01 (95% CI, 0.76-1.34)

• Primary Outcome: Duration of disease control: 22.8 months (Arm A) vs 23.5 months (Arm B)

• Nnt Or Sensitivity: No clinically meaningful difference between treatment strategies

• Confidence Interval: 95% CI: 0.76-1.34 for primary endpoint

Clinical Application

Both treatment strategies are feasible in tertiary oncology centres with access to targeted therapies Relevant to Australian practice where cetuximab and bevacizumab are PBS-listed for mCRC. Results support flexible sequencing approach based on patient factors rather than predetermined strategy Patients with untreated, unresectable wild-type RAS/BRAF metastatic colorectal cancer suitable for intensive combination therapy

Abstract

Managing unresectable metastatic colorectal cancer (mCRC) requires a comprehensive strategy. While chemotherapy, anti-angiogenic, and anti-epidermal growth factor receptor (EGFR) agents are available, strategy trials are needed to optimize their use and sequencing. The STRATEGIC-1 phase III trial (NCT01910610) was designed to determine the optimal treatment sequence in patients with untreated, unresectable wild-type RAS/BRAFV600E mCRC. Patients were randomized (1:1) to FOLFIRI-cetuximab then mFOLFOX6-bevacizumab (arm A) or OPTIMOX-bevacizumab then FOLFIRI-bevacizumab followed by EGFR monoclonal antibody +/- irinotecan (arm B). The primary endpoint was the duration of disease control (DDC). Secondary endpoints were overall survival (OS), time to failure of strategy (TFS), progression-free survival (PFS), overall response rate (ORR), salvage surgery rate, safety, and health-related quality of life (HRQoL). Overall, 263 patients (arm A:131, arm B:132) were randomized. After 68.4 months of median follow-up (95% CI, 76.5-98.0), the median DDC was 22.8 months (95% CI, 20.4-28.8) in arm A and 23.5 months (95% CI, 17.9-26.3) in arm B (HR = 1.01, 95% CI, 0.76-1.34; log-rank P = 0.945). The median OS was 40.4 months (95% CI, 32.4-51.1) in arm A and 34.4 months (95% CI, 27.5-42.2) in arm B (HR = 1.30, 95% CI, 0.99-1.72). The ORR was higher in arm A (82.4% versus 65.4%) in the first-line group but not in the second-line group (20.7% versus 16.4%). Adverse events were consistent with the well-known safety profiles. STRATEGIC-1 did not meet its primary endpoint and was inconclusive in identifying the optimal treatment strategy in wild-type RAS/BRAFV600E mCRC.

References

1. 1.Chibaudel, B., Dourthe, L. M., André, T., Henriques, J., Bourgeois, V., Etienne, P. L., Desramé, J., Carola, E., Dupuis, O., Baba-Hamed, N., Auby, D., Louvet, C., Maillard, E., Romano, O., Tournigand, C., Garcia-Larnicol, M. L., Shacham-Shmueli, E., Bird, B. H., Ghiringhelli, F., & de Gramont, A. (2026). STRATEGIC-1: multiple-line, randomized, open-label GERCOR-PRODIGE-39 phase III trial in unresectable RAS/BRAF wild-type metastatic colorectal cancer. Signal Transduction and Targeted Therapy. https://doi.org/10.1200/JCO.2011.35.5867