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A new targeted therapy is shaking up the standard of care for a common lung cancer subtype. The phase 3 Krascendo 1 trial found that divarasib cut the risk of death by 44% and extended overall survival by nearly 6 months compared to approved KRAS inhibitors sotorasib and adagrasib — with fewer serious side effects. Experts are calling it a likely new standard of care for KRAS G12C-mutated NSCLC.
A next-generation KRAS inhibitor is poised to redefine treatment for one of the most common lung cancer subtypes. Results from the randomized phase 3 Krascendo 1 trial — presented at the ESMO Congress and simultaneously published in the New England Journal of Medicine — showed that divarasib (Genentech/Roche) significantly outperformed the two currently approved KRAS G12C inhibitors, sotorasib and adagrasib, in patients with previously treated, locally advanced or metastatic NSCLC harboring a KRAS G12C mutation.
The trial enrolled 338 patients who had received one to three prior lines of therapy. Divarasib was given at 400 mg once daily, while the control arm received physician's choice of sotorasib or adagrasib. No crossover was permitted. While divarasib showed more gastrointestinal side effects overall — with diarrhea occurring in about two-thirds of patients — serious adverse events and treatment discontinuations were notably lower than in the control group.
By the Numbers:
Why it matters: KRAS G12C mutations affect 12–14% of nonsquamous NSCLC patients, and neither sotorasib nor adagrasib had demonstrated an OS benefit over docetaxel. Divarasib's survival advantage — paired with a more favorable tolerability profile — positions it as a likely new standard of care in this setting, with ongoing trials now exploring its role in first-line and adjuvant treatment.
