KRASCENDO 1
In previously treated KRAS G12C-mutated advanced NSCLC, does divarasib improve outcomes over sotorasib or adagrasib?
One underlying study; aliases and follow-up reports consolidated. Primary discipline: Medical.
338 adults with previously treated advanced/metastatic KRAS G12C-mutated NSCLC.
KRAS G12C-mutated disease after prior systemic therapy; divarasib remains investigational at this evidence cut-off.
338 (167 divarasib; 171 control) randomised/evaluable as reported.
Oral divarasib once daily.
Investigator-selected sotorasib once daily or adagrasib twice daily.
Endpoints and results
Primary BICR-assessed PFS; secondary OS, ORR, duration of response and safety.
- Median OS 17.7 vs 12.0 months; HR 0.56 (95% CI 0.41–0.78; p=0.0005).
- Median PFS 9.8 vs 5.7 months; HR 0.58 (95% CI 0.44–0.76; p<0.0001).
- 12-month PFS 44% vs 24%; ORR 58% vs 32%; median response duration 11.9 vs 6.9 months.
- Treatment-related discontinuation 4.8% vs 11.7%; serious treatment-related AEs 7.8% vs 15.2%.
Absolute Effect and outcome visualisation
12-month PFS
% progression-free at 12 months · 12 months. Bars show source-reported fixed-time percentages.
Interpretation: 20-point absolute difference in 12-month PFS; approximate landmark NNT 5 at 12 months, calculated from the fixed-time rates, not median PFS.
Toxicity, discontinuation and quality of life
Trial-specific harms: GI toxicity and hepatotoxicity; serious treatment-related AEs 7.8% vs 15.2%.
Treatment burden/discontinuation: Treatment-related discontinuation 4.8% vs 11.7%, despite longer exposure with divarasib (11.3 vs 5.0 months).
Quality of life: No definitive comparative QoL estimate is reproduced here.
Subgroups, maturity and limitations
Subgroups: Benefit reported across clinically relevant subgroups, including PD-L1 and KEAP1 status.
Maturity: Phase III primary analysis published in NEJM and presented at ESMO 2026.
Limitations: Open-label; investigator-selected active comparator. Divarasib remains investigational pending regulatory decisions.
A positive head-to-head phase III trial with PFS and OS superiority over current KRAS G12C inhibitors; availability and longer-term safety remain pending.
Use current regional guidelines, patient fitness, biomarkers, competing risks, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.
Primary sources and registry
Registry: NCT06497556
The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.