New targeted therapy improved survival for patients with KRAS-mutated lung cancer
· Medical Xpressby University of Texas MD Anderson Cancer Center
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Patients with previously treated advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC) lived significantly longer and saw improved disease control when treated with the next-generation KRAS-targeted therapy divarasib, according to researchers from The University of Texas MD Anderson Cancer Center.
Results from the global Phase III Krascendo 1 study were published in The New England Journal of Medicine and presented at the European Society for Medical Oncology (ESMO) Congress 2026. The study was led by principal investigator Ferdinandos Skoulidis, M.D., Ph.D., professor of Thoracic/Head and Neck Medical Oncology.
In the trial, researchers compared divarasib with two currently approved KRAS G12C inhibitors, sotorasib or adagrasib, in NSCLC patients whose cancer had progressed after prior treatment. Treatment with divarasib reduced the risk of disease progression by 42% and the risk of death by 44%. Median overall survival improved with divarasib to 17.7 months versus 12 months with sotorasib/adagrasib.
"For patients with KRAS G12C-mutant lung cancer, extending survival and delaying cancer progression are the outcomes that matter most," Skoulidis said. "Divarasib significantly improved both measures compared with currently available KRAS inhibitors. These results establish divarasib as a new standard of care and offer hope for patients whose treatment options have been limited after their cancer progresses."
Blocking the signal driving cancer growth
KRAS is one of the most commonly altered genes in NSCLC, and these mutations allow cancer cells to grow uncontrollably. Approximately 14% of patients with NSCLC have a specific type of mutation, known as KRAS G12C.
While KRAS was once thought to be undruggable, in recent years, KRAS G12C inhibitors (including sotorasib and adagrasib) became the first approved therapies designed to specifically target the mutation.
Divarasib is a next-generation oral targeted therapy designed to block KRAS G12C more effectively than the therapies that are currently approved. The treatment works by locking the abnormal KRAS protein in an inactive state, essentially switching off a key signal that cancer cells depend on to grow and survive.
Head-to-head trial shows longer disease control
Krascendo 1 is the first Phase III trial to directly compare a next-generation KRAS inhibitor with approved KRAS-targeted treatments, providing important evidence about whether a newer generation of these medicines can help patients live longer.
The trial enrolled 338 patients with previously treated advanced or metastatic KRAS G12C-mutant NSCLC at 151 centers across 26 countries. Participants were randomly assigned to receive divarasib, sotorasib or adagrasib.
After a median follow-up of 14.3 months, patients treated with divarasib experienced a median progression-free survival of 9.8 months compared with 5.7 months for those receiving standard KRAS inhibitors. At one year, 44% of patients receiving divarasib remained free from disease progression or death versus 24% of those in the control group.
On top of the improved overall survival, patients were nearly twice as likely to respond to treatment with divarasib versus the control treatment. The overall response rate was 58.4% compared with 32.3% for standard therapy, and responses lasted longer, with a median duration of response of 11.9 months versus 6.9 months.
Fewer severe side effects, with study caveats
Improved efficacy did not come at the cost of increased toxicity. Divarasib was better tolerated, with severe treatment-related side effects occurring in 25% of patients compared with 35% of those receiving current KRAS-targeted therapies, despite patients receiving divarasib treatment for twice as long.
Limitations of the study include its open-label design and the relatively small number of patients in the control group who received adagrasib. In addition, patients with untreated brain metastases were not eligible for enrollment.
Publication details
Ferdinandos Skoulidis et al., Divarasib as Compared with Sotorasib or Adagrasib in KRAS G12C–Mutated NSCLC, New England Journal of Medicine (2026). DOI: 10.1056/nejmoa2605703
Journal information: New England Journal of Medicine
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Citation: New targeted therapy improved survival for patients with KRAS-mutated lung cancer (2026, October 26) retrieved 27 October 2026 from https://medicalxpress.com/news/2026-10-therapy-survival-patients-kras-mutated.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.