The US FDA has approved the combination therapy of sotorasib (Lumakras) and panitumumab (Vectibix) for adult patients with metastatic colorectal cancer (mCRC) harboring KRAS G12C mutations.

Grade 3-4 laboratory abnormalities noted during the trial included decreased magnesium, potassium, and corrected calcium levels, as well as increased potassium, impacting two or more patients.

Patients receiving the combination therapy experienced a median PFS of 5.6 months, significantly better than the 2 months observed in those on standard care.

The recommended dosing regimen includes 960 mg of sotorasib taken orally once daily and 6 mg/kg of panitumumab administered as an IV infusion every 14 days until disease progression or unacceptable toxicity occurs.

Common adverse reactions associated with this combination therapy included rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain, all occurring in at least 20% of patients.

Despite the positive PFS results, the final analysis indicated no significant difference in overall survival (OS) between the treatment arms, as the study was not statistically powered for OS outcomes.

This approval stems from the promising results of the CodeBreaK 300 trial, which highlighted improved overall response rates (ORR) and progression-free survival (PFS) compared to standard treatments such as trifluridine/tipiracil or regorafenib.

In the trial, the ORR for the sotorasib/panitumumab group was 26%, while the standard care group recorded a 0% ORR, with the treatment arm showing a duration of response of 4.4 months.

This treatment is specifically indicated for patients who have previously undergone chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan.