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Matching-Adjusted Indirect Comparison of Sotorasib Plus Panitumumab Versus Trifluridine/Tipiracil Plus Bevacizumab in Chemorefractory Metastatic Colorectal Cancer

Year: 2026

Type: article

Abstract: BACKGROUND: Sotorasib 960 mg plus panitumumab (soto960+pani) was investigated in chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC) in the phase 3 CodeBreaK 300 and phase 1b CodeBreaK 101 studies. In CodeBreaK 300, soto960+pani significantly improved progression-free survival (PFS) versus investigator's choice therapy (trifluridine/tipiracil [T/T] or regorafenib). The phase 3 SUNLIGHT study evaluated T/T plus bevacizumab (T/T+bev) in patients with unselected refractory mCRC and found longer survival times with T/T+bev than T/T monotherapy. Matching-adjusted indirect treatment comparisons (MAIC) were performed to compare the efficacy and safety of soto960+pani with new standard-of-care T/T+bev treatment. MATERIALS AND METHODS: Clinical outcomes and adverse events (AEs) from CodeBreaK 300 and 101 (for soto960+pani) were compared with those from SUNLIGHT (for T/T+bev). By reweighting individual patient-level data from the pooled CodeBreaK studies, differences in baseline characteristics were adjusted. Odds ratios (ORs) were estimated for objective response rates; hazard ratios (HRs) were used for PFS and overall survival (OS). RESULTS: From a pool of 93 patients, the effective sample size of soto960+pani with matched characteristics was 29 patients. Soto960+pani increased the likelihood of treatment response, with an adjusted OR of 5.7 (95% CI, 2.6-12.8) versus T/T+bev. HR for PFS was 0.77 (95% CI, 0.47-1.25); HR for OS was 0.44 (95% CI, 0.22-0.87), suggesting a survival benefit favoring soto960+pani. Grade ≥ 3 AEs occurred in 58% and 72% of soto960+pani-treated and T/T+bev-treated patients, respectively. CONCLUSION: In this MAIC analysis, soto960+pani demonstrated statistically significant improvement in response rates and OS in patients with chemorefractory KRAS G12C-mutated mCRC.

Source: Clinical Colorectal Cancer

DOI: 10.1016/j.clcc.2026.04.003