Gilberto Lopes, Chief of the Division of Medical Oncology at the Sylvester Comprehensive Cancer Center, shared on LinkedIn:
“Krascendo 1 at ESMO 2026
A new generation of KRAS inhibitors delivers better survival in lung cancer.
Today, the phase III Krascendo 1 results were presented at ESMO and simultaneously published in the New England Journal of Medicine.
This is an important trial because it directly compared the next-generation KRAS G12C inhibitor divarasib against existing targeted treatments, sotorasib or adagrasib, in previously treated advanced KRAS G12C-mutated NSCLC.
Among 338 randomized patients, the results were compelling:
- Median overall survival: 17.7 vs 12.0 months, HR 0.56 (95% CI 0.41–0.78; P=0.0005)
- Median progression-free survival: 9.8 vs 5.7 months, HR 0.58 (95% CI 0.44–0.76; P<0.0001)
- Objective response rate: 58.4% vs 32.3%
And importantly, superior efficacy was not accompanied by greater toxicity.
Serious treatment-related adverse events occurred in 7.8% versus 15.2%, while discontinuations due to treatment-related adverse events occurred in 4.8% versus 11.7%.
Three observations stand out.
- First, this is the kind of evidence we need to advance targeted cancer therapy: randomized comparisons against active drugs, not just historical controls.
- Second, improvement in overall survival establishes a particularly compelling argument for clinical benefit.
- Third, the apparent improvement in tolerability suggests that newer targeted therapies may improve both efficacy and the treatment experience.
But several questions remain.
The comparator group included relatively few patients receiving adagrasib. Patients with untreated brain metastases were excluded. We also need longer follow-up and better understanding of resistance, subsequent therapy, and intracranial efficacy.
And divarasib is still investigational, pending regulatory review. The next frontier is moving these advances earlier in the disease course and learning how to overcome resistance.
Krascendo 2 and 3 will investigate first-line and adjuvant strategies, respectively.
Congratulations to Ferdinandos Skoulidis and the investigators, patients, and research teams involved.
This is meaningful progress for patients with KRAS G12C-mutated lung cancer.
Skoulidis et al. New England Journal of Medicine. October 25, 2026.”
Title: Krascendo 1: Efficacy and safety of divarasib (diva) vs sotorasib (soto) or adagrasib (ada) in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC
Authors: Ferdinandos Skoulidis, Myung-Ju Ahn, Shirish Gadgeel, Sanjay Popat, Niels Reinmuth, Bianca Van Veggel, Farastuk Bozorgmehr, Victoria J. Bray, Michael Duruisseaux, Wade T. Iams, Julien Mazieres, Laura Bonanno, Lore Decoster, Bo Wang, Youyou Hu, Sarah M. Shagan, Verena Lam, Uyi Osaghae, Tien Hoang
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