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Commentary|Videos|November 4, 2026
How Does Divarasib Compare With Other KRAS Inhibitors in NSCLC?
Author(s)Ferdinandos Skoulidis, MD, PhD
Fact checked by: Matt Flowers
Key Takeaways
- Divarasib achieved a higher ORR than sotorasib or adagrasib (58% vs 32%) in previously treated KRAS G12C-mutated NSCLC.
- Median duration of response was longer with divarasib (11.9 vs approximately 6.9 months).
Divarasib’s ORR was 58% vs 32% for sotorasib or adagrasib in the phase 3 Krascendo 1 trial. Dr Skoulidis discusses response, durability, and survival.
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The investigational KRAS G12C inhibitor divarasib demonstrated a higher objective response rate and longer duration of response than currently available KRAS-targeted therapies in patients with previously treated advanced or metastatic non–small cell lung cancer (NSCLC), according to findings from the
In this video interview, Ferdinandos Skoulidis, MD, PhD, highlights the importance of these efficacy findings, particularly for patients with advanced disease who may have substantial tumor burden and significant symptoms.
The confirmed objective response rate (ORR) with divarasib was 58% compared with 32% in patients receiving sotorasib (Lumakras) or adagrasib (Krazati). Skoulidis, a professor of Thoracic/Head and Neck Medical Oncology UT MD Anderson Cancer Center, emphasizes that tumor shrinkage is an important treatment goal for symptomatic patients, making ORR a clinically meaningful measure of treatment activity.
He also notes that responses with divarasib were rapid, deep, and durable. The median duration of response was 11.9 months with divarasib compared with approximately 6.9 months with sotorasib or adagrasib, representing another efficacy measure favoring the investigational agent.
The phase 3 Krascendo 1 trial directly compared divarasib with sotorasib or adagrasib in 338 patients with previously treated advanced or metastatic KRAS G12C-mutated NSCLC. Beyond the response findings discussed by Skoulidis, the study demonstrated improvements in progression-free survival (PFS) and overall survival (OS). Median PFS was 9.8 months with divarasib vs 5.7 months with standard KRAS inhibitors. Median OS was 17.7 months vs 12 months, respectively. Divarasib also reduced the risk of disease progression by 42% and the risk of death by 44%.
Together, these findings highlight the potential of next-generation KRAS G12C inhibition to improve outcomes for patients whose disease has progressed after prior treatment. Skoulidis' discussion underscores why response rate and response durability are important considerations as newer targeted therapies are evaluated against existing treatment options.
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