Metastatic colorectal cancer (CRC) patients with KRAS (G12C) mutations benefit from sotorasib plus panitumumab
Kirsten rat sarcoma viral oncogene homologs are present in approximately 3% of all metastatic colorectal tumors (class) gly12-to-cys (G12C) mutation. Associated with poor prognosis.1 Sotorasib is a selective KRAS inhibitor that targets proteins derived from KRAS. class (G12C) mutation. In the Phase 1b CodeBreak 101 trial (NCT04185883), the combination of sotorasib and the epidermal growth factor receptor (EGFR) inhibitor panitumumab showed a promising objective response rate (ORR, 30%) in participants with advanced disease. class (G12C) Mutant colorectal cancer (CRC).2 The current CodeBreak 300 trial (NCT05198934) is a randomized phase 3 trial to further investigate the clinical efficacy and safety of the combination of sotorasib and panitumumab in participants with the following conditions: class (G12C) Mutant CRC. Dr. Filippo Pietrantonio of National Institute of Oncology, Italypublished the first results.3
The study enrolled 159 participants who had received at least one type of treatment for metastatic colorectal cancer. Participants received 3 arms: sotorasib 960 mg daily + panitumumab (arm A), sotorasib 240 mg daily + panitumumab (arm B), or a control group (investigator’s choice: trifluridine/tipiracil or regorafenib). randomly assigned. The primary endpoint of the study was progression-free survival (PFS).
After a median follow-up of 7.8 months, the combination of sotorasib (both doses) and panitumumab significantly improved PFS. Median PFS was 5.6 months in group A, 3.9 months in group B, and 2.2 months in control group (group A: HR, 0.48; 95% CI, 0.30 to 0.80; 95% CI, 0.30 to 0.80; CI, 0.30-0.80). P=.006, Arm B: HR, 0.58. 95% CI, 0.36-0.93; P=.30, both for control arms). PFS benefits were seen in all prespecified subgroups. ORR was significantly improved by 26% in group A, 6% in group B, and 0% in the control group. Overall survival data were not mature at the data cutoff date. “Both doses of sotorasib in combination with panitumumab were well tolerated, with no new safety signals or fatal treatment-related adverse events, supporting a dose of 960 mg daily of sotorasib in CRC.” emphasized Dr. Pietrantonio.
These data suggest that the combination of sotorasib and panitumumab may become a new standard of care for previously treated patients. class (G12C) Mutant metastatic CRC. “But overall survival data will have to wait,” warned discussant Dr. Miriam Koopman of Utrecht University Medical Center in the Netherlands.
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