Sotorasib plus panitumumab may be a promising treatment option for colorectal cancer

1. While not statistically significant, the use of sotorasib plus panitumumab may have a 30% relative risk reduction in the risk of death compared to the investigator’s choice of chemotherapy in the management of Kirsten rat sarcoma viral oncogene homologue (KRAS) glycine-to-cysteine mutation at codon 12 (KRAS G12C) colorectal cancer.

Evidence Rating Level: 1 (Excellent)

Currently, the management of KRAS-mutated colorectal cancer remains limited to chemotherapy with a lack of targeted therapeutic options available. CodeBreak 300 was a randomized, phase III clinical trial which evaluated the efficacy of sotorasib, an irreversible KRAS G12C inhibitor, in combination with panatimumab compared to the investigator’s choice of standard-care trifluridine/tipiracil or regorafinib. This study presents the final analysis of overall survival (OS) of CodeBreak 300. 160 patients with KRAS G12C chemorefractory metastatic colorectal cancer (mCRC) were randomly assigned to receive either sotorasib 960 mg-panatimumab (n = 53), sotorasib 240 mg-panatimumab (n = 53) or investigator’s choice (n = 54). The estimated hazard ratio (HR) for OS was 0.83 (95% CI, 0.49 to 1.39; descriptive two-sided P = .50) with sotorasib 240 mg-panatimumab and 0.70 (95% CI, 0.41 to 1.18; two-sided P = .20 v statistically significance threshold 0.01875) with sotorasib 960 mg-panatimumab. The overall response rates (ORR) across the sotorasib 960 mg-panatimumab, sotorasib 240 mg-panatimumab, and investigator’s choice groups were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9). Overall, this study found that while there was no statistically significant difference in OS between each of the groups, the use of sotorasib 960 mg plus panitumumab may have a 30% relative risk reduction in the risk of death compared to the use of trifluridine/tipiracil or regorafinib. 

Click to read the study in JCO

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