Treatment with sotorasib, an oral KRAS G12C inhibitor, was associated with superior progression-free survival and overall response rate when compared with standard-of-care docetaxel for patients with previously treated non-small cell lung cancer, according to phase 3 study results presented at the ESMO Congress 2022.

“This represents a major advance for the treatment of patients with KRAS G12C-mutated NSCLC and reinforces the importance of next-generation sequence testing to inform treatment decisions for patients with NSCLC,” said Melissa L. Johnson, MD, associate director of lung cancer research at Sarah Cannon Research Institute, Nashville, in a press release.

In the CodeBreaK 200 clinical trial, patients with NSCLC and a confirmed KRAS G12C mutation were randomly assigned to oral sotorasib (960 mg per day) or to intravenous docetaxel (75 mg/m²) after disease progression following treatment with chemoimmunotherapy.

PFS served as the study’s primary endpoint, with ORR, disease control rate, overall survival, and safety serving as secondary endpoints. The study included data from 345 patients who were randomly assigned to treatment in a 1:1 ratio. With a median follow-up of 17.7 months, the study showed a significant PFS improvement in patients assigned to sotorasib (HR = 0.66; 95% CI, 0.51-0.86; P = .002). The 1-year PFS in the sotorasib arm was 24.8%, compared with 10.1% in the docetaxel arm.

Treatment with sotorasib was further associated with a significant improvement in ORR (28.1% vs 13.2%; P < .001). The disease control rate in the sotorasib arm was 82.5%, compared with 60.3% in the docetaxel arm. Compared with docetaxel, patients assigned to sotorasib experienced fewer any-grade adverse events (70.4% vs 86.1%), grade 3 or higher adverse events (33.1% vs 40.4%), and serious adverse events (10.7% vs 22.5%). Sixteen patients assigned to sotorasib and 17 patients assigned to docetaxel discontinued treatment due to adverse events.

OS results did not reach statistical significance, according to the researchers, who noted that the study was not powered to evaluate OS. Due to the benefits associated with sotorasib, and per regulatory guidance, the researchers reduced the study’s planned enrollment and allowed patients in the docetaxel arm to cross over following disease progression.

“To date, these results confirm sotorasib as second-line therapy for patients with NSCLC harboring KRAS G12C mutations, and that further improvements are highly required for this specific molecular-driven patient population, where different kinds of combinations are under evaluation to overcome resistance and improve the modest efficacy of monotherapy,” said Antonio Passaro, MD, PhD, a thoracic oncologist from the Istituto Europeo di Oncologia, Milan, who was not involved in the study. 

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Disclosures: Johnson declared financial ties to drugmakers. See full abstract for details. CodeBreaK 200 was supported by Amgen.