Results from a phase 3 trial have shown that sotorasib combined with panitumumab may serve as an effective strategy for patients with metastatic colorectal cancer (CRC) with KRAS G12C mutations. While KRAS G12C mutations occur in 3% to 4% of patients with metastatic CRC, monotherapy treatments have yielded only average results.
This multicenter, open-label, randomized trial led by Dr. Marwan G. Fakih, of City of Hope Comprehensive Cancer Center, examined the treatment combination in patients with chemorefractory metastatic CRC with mutated KRAS G12C who had not undergone previous treatment with a KRAS G12C inhibitor.
Patients were randomized to receive either sotorasib 90 mg once daily plus panitumumab (53 patients), sotorasib 240 mg once daily plus panitumumab (53 patients), or a standard treatment of trifluridine-tipiracil or regorafenib (54 patients).
The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and objective response (OR). After a median follow-up of 7.8 months, the median PFS was 5.6 months (95% CI, 4.2-6.3) in the sotorasib 960 mg/panitumumab arm and 3.9 months (95% CI, 3.7-5.8) in the sotorasib 240 mg/panitumumab arm compared with 2.2 months (95% CI, 1.9-3.9) in the standard treatment arm.
The hazard ratio (HR) for disease progression or death in the sotorasib 960 mg/panitumumab arm compared with the standard care arm was 0.49 (95% CI, 0.30-0.80; P=.006), and the HR in the sotorasib 240 mg/panitumumab arm was 0.58 (95% CI, 0.36-0.93; P=.03). The OR was 26.4% (95% CI, 15.3-40.3), 5.7% (95% CI, 1.2-15.7), and 0% (95% CI, 0.0-6.6) in the sotorasib 960 mg/panitumumab, sotorasib 240 mg/panitumumab, and standard care groups, respectively. OS data are still maturing.
Both doses of sotorasib in combination with panitumumab resulted in longer PFS than standard treatment, and toxic effects remained similar to both agents alone, resulting in few treatment discontinuations.
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