For patients with chemorefractory metastatic colorectal cancer, the KRAS G12C inhibitor sotorasib in combination with the epidermal growth factor receptor inhibitor panitumumab results in longer progression-free survival than standard treatment, according to a study published online Oct. 22 in the New England Journal of Medicine. The research was published to coincide with the annual meeting of the European Society for Medical Oncology, held from Oct. 20 to 24 in Madrid.
Marwan G. Fakih, M.D., from the City of Hope Comprehensive Cancer Center in Duarte, California, and colleagues randomly assigned patients with chemorefractory metastatic colorectal cancer with mutated KRAS G12C who had not received previous treatment with a KRAS G12C inhibitor to receive sotorasib 960 mg once daily plus panitumumab, sotorasib 240 mg once daily plus panitumumab, or the investigator’s choice of trifluridine-tipiracil or regorafenib (standard care; 53, 53, and 54 patients, respectively).
The researchers found that the median progression-free survival was 5.6 and 3.9 months versus 2.2 months in the 960-mg and 240-mg sotorasib-panitumumab groups, respectively, versus the standard-care group after a median follow-up of 7.8 months. The hazard ratio for disease progression or death was 0.49 and 0.58 in the 960-mg and 240-mg sotorasib-panitumumab groups, respectively, compared with the standard-care group. In the 960-mg and 240-mg sotorasib-panitumumab groups and the standard-care group, the objective response rate was 26.4, 5.7, and 0 percent, respectively. Overall, treatment-related adverse events of grade 3 or higher occurred in 35.8, 30.2, and 43.1 percent, respectively.
“These findings are important in the context of the poor survival outcomes associated with KRAS G12C mutation in patients with colorectal cancer,” the authors write.
Several authors disclosed ties to pharmaceutical companies, including Amgen, which manufactures sotorasib and panitumumab and funded the study.
Marwan G. Fakih et al, Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2308795
New England Journal of Medicine
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