Divarasib as Compared with Sotorasib or Adagrasib in KRAS G12C-Mutated NSCLC
In brief
Divarasib extended median progression-free survival by 4.1 months in KRAS-mutated lung cancer
In a phase 3 trial of previously treated advanced lung cancer, divarasib extended median progression-free survival to 9.8 months versus 5.7 months with sotorasib or adagrasib, and median overall survival to 17.7 versus 12.0 months. Tumors responded in 58% of patients on divarasib versus 32% on control, with fewer severe treatment-related side effects; follow-up was 14.3 months.
- Journal
- The New England journal of medicine (Q1)
- Published
- 25 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Ferdinandos Skoulidis, Myung-Ju Ahn, Shirish Gadgeel, Sanjay Popat, Niels Reinmuth, Bianca van Veggel, et al.
- PMID
- 42929675
- DOI
- 10.1056/NEJMoa2605703
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 8 November 2026): Phase III RCT, improved PFS and OS
Abstract
BACKGROUND: Divarasib, a next-generation, oral KRAS G12C inhibitor, is more potent and selective in vitro than the first-generation KRAS G12C inhibitors sotorasib and adagrasib. METHODS: In this phase 3, international, open-label trial, patients with previously treated KRAS G12C-mutated advanced or metastatic non-small-cell lung cancer (NSCLC) were randomly assigned to receive divarasib orally at a dose of 400 mg once daily or control treatment (sotorasib orally at a dose of 960 mg once daily or adagrasib orally at a dose of 600 mg twice daily) until the occurrence of disease progression, unacceptable adverse events, loss of clinical benefit, withdrawal of consent, death, or trial termination. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included overall survival, confirmed overall response, duration of response, patient-reported outcomes, and safety. RESULTS: A total of 338 patients received divarasib (167 patients) or control treatment (171 patients; 156 received sotorasib and 15 received adagrasib). The median follow-up was 14.3 months. The median progression-free survival was 9.8 months with divarasib and 5.7 months with control treatment (hazard ratio for disease progression or death, 0.58; 95% confidence interval [CI], 0.44 to 0.76; P<0.001). The median overall survival was 17.7 months with divarasib and 12.0 months with control treatment (hazard ratio for death, 0.56; 95% CI, 0.41 to 0.78; P<0.001). Of the 328 patients who could be evaluated for response, a confirmed response occurred in 58.4% in the divarasib group and in 32.3% in the control group. The median duration of response was 11.9 months with divarasib and 6.9 months with control treatment. Fewer grade 3 or 4 treatment-related adverse events were noted with divarasib (24.6%) than with control treatment (34.5%). CONCLUSIONS: Among patients with previously treated KRAS G12C-mutated advanced or metastatic NSCLC, divarasib led to significantly longer progression-free and overall survival than control treatment. (Supported by F. Hoffmann-La Roche; Krascendo 1 ClinicalTrials.gov number, NCT06497556.).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.