On January 16, 2025, the Food and Drug Administration sanctioned the use of sotorasib (Lumakras, Amgen Inc.) in conjunction with panitumumab (Vectibix, Amgen Inc.) for adult patients diagnosed with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as identified by an FDA-approved assay, who have previously undergone treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Today, the FDA authorized the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic tool to assist in identifying colorectal cancer patients with KRAS G12C mutations who may qualify for Lumakras in conjunction with Vectibix.
Effectiveness and Safety
The efficacy was assessed in CodeBreaK 300 (NCT05198934), a randomized, open-label, controlled trial involving patients with KRAS G12C-mutated metastatic colorectal
cancer who had previously undergone treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. Mutations were systematically detected in
tumor tissue samples utilizing the QIAGEN therascreen KRAS RGQ PCR kit.
One hundred sixty patients were randomized (1:1:1) to receive either sotorasib 960 mg orally once daily with panitumumab 6 mg/kg intravenously every two weeks, sotorasib 240 mg orally once daily with panitumumab 6 mg/kg intravenously every two weeks, or the investigator’s choice of standard of care, which included trifluridine/tipiracil or regorafenib.
The primary effectiveness endpoint was progression-free survival (PFS), assessed by blinded independent central review in accordance with
RECIST v1.1. Supplementary efficacy outcome variables encompassed overall survival (OS), overall response rate (ORR), and duration of response (DOR). The study lacked sufficient statistical power for overall survival (OS).
The median progression-free survival (PFS) was 5.6 months (95% confidence interval: 4.2, 6.3) in the sotorasib 960 mg/panitumumab group and 2 months (95% confidence interval: 1.9, 3.9) in the standard of care group, with a hazard ratio of 0.48 (95% confidence interval: 0.3, 0.78) and a two-sided p-value of 0.005. The ultimate analysis of overall survival was not statistically significant.
The overall response rate (ORR) was 26% (95% CI: 15, 40) in the sotorasib 960 mg/panitumumab group and 0% (95% CI: 0, 7) in the standard of care (SOC) group. The median duration of response (DOR) was 4.4 months (range: 1.9+, 6+) in the sotorasib 960 mg/panitumumab cohort.
The conclusive analysis of progression-free
survival for patients assigned to the sotorasib 240 mg/panitumumab group against the standard of care group was not statistically significant.
The predominant adverse effects (≥20%) associated with sotorasib 960 mg/panitumumab included rash, xerosis, diarrhea, stomatitis, weariness, and musculoskeletal pain. The predominant Grade 3-4 laboratory abnormalities observed in two or more individuals included hypomagnesemia, hypokalemia, hypocalcemia, and hyperkalemia.
The advised dosage of sotorasib is 960 mg administered orally once daily. The advised dosage of panitumumab is 6 mg/kg, delivered via IV infusion biweekly until
disease progression, intolerable toxicity, or the cessation of sotorasib. Administer the initial dosage of sotorasib prior to the first infusion of panitumumab.
