Discussion
gastrointestinal AEs, CRC, rash
The The combination of divarasib and cetuximab appeared to be well tolerated, and AEs were manageable with supportive medications and dose modifications. The most common AEs observed in this study were low-grade gastrointestinal AEs and rash, which were consistent with single-agent divarasib and cetuximab safety profiles, respectivelyThe improved antitumor activity observed with divarasib plus cetuximab in this study compared with single-agent divarasib is consistent with the hypothesis of EGFR-mediated adaptive feedback reactivation of the RAS–MAPK pathway following KRAS G12C inhibition. In patients with CRC who had not received prior KRAS G12C inhibitor treatment, single-agent divarasib achieved a response rate of 35.9%Divarasib has been shown to be 5 to 20 times more potent in vitro as compared to sotorasib and adagrasibDivarasib plus cetuximab treatment led to a decrease in In conclusion, divarasib in combination with cetuximab demonstrated a manageable safety profile and promising clinical activity. The further improvements in antitumor activity demonstrated with the addition of cetuximab to divarasib may represent an effective strategy for overcoming resistance to KRAS G12C inhibitors. Divarasib is continuing to be investigated with other anticancer therapies for patients with CRC in this study, including bevacizumab, GDC-1971 (a SHP2 inhibitor) and inavolisib (a PI3Kα inhibitor). Additionally, a study is ongoing to explore the effects of the combination of divarasib plus cetuximab with or without chemotherapy (FOLFOX: 5-FU, leucovorin and oxaliplatin; or FOLFIRI: leucovorin, 5-FU and irinotecan; ClinicalTrials.gov: 