The phase III CodeBreaK 300 trial showed that sotorasib plus panitumumab improved progression-free survival vs standard care in patients with KRAS G12C–mutated refractory metastatic colorectal cancer. Findings were presented at the European Society for Medical Oncology (ESMO) Congress 2023 (LBA10) and reported in The New England Journal of Medicine by Marwan Fakih, MD, and colleagues.
Marwan Fakih, MD
Study Details
In the open-label trial, 160 patients enrolled from sites in 12 countries between April 2022 and March 2023 were randomly assigned 1:1:1 to receive sotorasib at 960 mg once daily plus panitumumab at 6 mg/kg every 2 weeks (n = 53), sotorasib at 240 once daily plus panitumumab (n = 53), or standard care (n = 54) with investigator’s choice of either trifluridine/tipiracil (35 mg/m2 on days 1–5 and 8–12 every 28 days; n = 37) or regorafenib (160 mg once daily on days 1–21 every 28 days; n = 14). Patients had not received previous treatment with a KRAS G12C inhibitor. The primary endpoint was progression-free survival on blinded independent central review.
Progression-Free Survival
Median follow-up was 7.8 months (range = 0.1–13.9 months). Median progression-free survival was 5.6 months (95% confidence interval [CI] = 4.2–6.3 months) in the sotorasib 960-mg group (hazard ratio [HR] vs standard care = 0.49, 95% CI = 0.30–0.80, P = .006), 3.9 months (95% CI = 3.7–5.8 months) in the sotorasib 240-mg group (HR vs standard care = 0.58, 95% CI = 0.36–0.93, P = .03), compared with 2.2 months (95% CI = 1.9–3.9 months) in the standard-care group.
Objective response rates were: 26.4% (including 1 complete response) in the sotorasib 960-mg group, 5.7% in the sotorasib 240-mg group, and 0% in the standard care group. Disease control rates were 71.7%, 67.9%, and 46.3%, respectively.
KEY POINTS
- Sotorasib at 960 mg and 240 mg combined with panitumumab prolonged progression-free survival vs standard care.
- Median progression-free survival was 5.6 months and 3.9 months vs 2.2 months.
Adverse Events
Treatment-related grade ≥ 3 adverse events occurred in 35.8% of patients in the sotorasib 960-mg group, 30.2% of those in the sotorasib 240-mg group, and 43.1% of those in the standard-care group. The most common treatment-related adverse events of any grade in the sotorasib groups were hypomagnesemia (28.3% and 30.2%), rash (28.3% and 24.5%), and dermatitis acneiform (22.6% and 37.7%).
Treatment-related serious adverse events occurred in 5.7%, 0%, and 7.8% of patients in the three groups. Treatment-related adverse events led to discontinuation of any study drug in 3.8%, 1.9%, and 2.0%. No treatment-related deaths were reported.
The investigators concluded, “In this phase III trial of a KRAS G12C inhibitor plus an EGFR inhibitor in patients with chemorefractory metastatic colorectal cancer, both doses of sotorasib in combination with panitumumab resulted in longer progression-free survival than standard treatment. Toxic effects were as expected for either agent alone and resulted in few discontinuations of treatment.”
Dr. Fakih, of City of Hope Comprehensive Cancer Center, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Amgen. For full disclosures of the study authors, visit nejm.org.
