Sotorasib combined with panitumumab in the treatment of mutant refractory colorectal cancer KRASG12C

KRASG12C is a mutation that occurs in about 3-4% of patients with metastatic colorectal cancer. Monotherapy with KRAS G12C inhibitors produced only moderate efficacy. Combining the KRAS G12C inhibitor sotorasib with the epidermal growth factor receptor (EGFR) panitumumab panitumumab may be an effective strategy.

In this phase , multicenter, open-label, randomized trial, we classified patients with chemotherapy-refractory metastatic colorectal cancer as having mutant KRAS not previously receiving KRAS G12Cpatients treated with G12Cinhibitors received a dose of 960 mgOnce-daily sotolacil combined with panitumumab treatment(53patients)received a dose of 240 mgOnce-daily sotolacil plus panitumumab(53patients), or trifluridine of the investigator's choice-Tipiracil or regorafenib treatment(standard treatment; 54patients). The primary endpoint was progression-free survival by blinded independent central review according to Response Evaluation Criteria in Solid Tumors (version 1.1). Key secondary endpoints are overall survival and objective response.

After a median follow-up of 7.8 months (range 0.1 to 13.9) , the 960-mg sotorasib-panitumumab group and240-mg The median progression-free survival in the sotorasib-panitumumab group was 5.6 months (95% confidence interval [ CI]is4.2 to 6.3) and 3.9 months (95% CI was 3.7 to 5.8), while the control group was 2.2 months(95% CIwas 1.9 to 3.9)The hazard ratio for disease progression or death in the 960 mg sotorasib–panitumumab group compared with the standard treatment group was 0.49 (95% The hazard ratio for the 240-mg sotorasib–panitumumab group was 0.58 (95% CI, 0.36 to 0.93; P=0.03). Overall survival data are maturing. The objective response rate was 26.4% (95%) in the 960 mg sotorasib–panitumumab group, the 240 mg sotorasib–panitumumab group, and the standard treatment group, respectively. CI, 15.3 to 40.3) , 5.7% (95% CI, 1.2 to 15.7) and 0% (95% CI, 0.0 to 6.6). Treatment-related adverse events of grade 3 or higher occurred in 35.8%, 30.2%, and 43.1% of patients, respectively. Skin-related toxicities and hypomagnesemia aresotorasib–panitumumabMost common adverse events.

In a phase 3 clinical trial of a KRAS G12C inhibitor plus an EGFR inhibitor in patients with chemotherapy-refractory metastatic colorectal cancer, two doses of sotoracil combined with panitumumab resulted in longer progression-free survival than standard treatment. Either drug used alone will produce expected toxic effects and result in few treatment interruptions.