Outcomes of Patients With Advanced NSCLC From the Intergroupe Francophone de Cancérologie Thoracique Biomarkers France Study by KRAS Mutation Subtypes

Anne-Marie Ruppert, Michèle Beau-Faller, Didier Debieuvre, L'Houcine Ouafik, Virginie Westeel, Isabelle Rouquette, Julien Mazières, Pierre-Paul Bringuier, Isabelle Monnet, Fabienne Escande, Charles Ricordel, Jean-Philippe Merlio, Henri Janicot, Antoinette Lemoine, Pascal Foucher, Michel Poudenx, Franck Morin, Alexandra Langlais, Pierre-Jean Souquet, Fabrice Barlesi, Marie Wislez, Anne-Marie Ruppert, Michèle Beau-Faller, Didier Debieuvre, L'Houcine Ouafik, Virginie Westeel, Isabelle Rouquette, Julien Mazières, Pierre-Paul Bringuier, Isabelle Monnet, Fabienne Escande, Charles Ricordel, Jean-Philippe Merlio, Henri Janicot, Antoinette Lemoine, Pascal Foucher, Michel Poudenx, Franck Morin, Alexandra Langlais, Pierre-Jean Souquet, Fabrice Barlesi, Marie Wislez

Abstract

Introduction: KRAS mutations are detected in 20% to 30% of NSCLC. However, KRAS mutation subtypes may differently influence the outcome of patients with advanced NSCLC.

Methods: In the Biomarkers France study, 4894 KRAS mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the KRAS mutations subtype.

Results: Over 95% of patients with KRAS mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with KRAS-mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5-9.5), without any differences according to the different KRAS subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2-5.1) for first-line treatment and 4.8 months (95% CI: 4.3-6.8) for second-line treatment, without any differences according to the different KRAS subtypes mutations.

Conclusions: KRAS mutation subtypes influenced neither treatment responses nor outcomes. The KRAS G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.

Keywords: KRAS mutation; NSCLC; Non–small cell lung cancer; Prognosis.

© 2020 The Authors.

Figures

Figure 1
Figure 1
Flow chart exhibiting patient selection.
Figure 2
Figure 2
Distribution of KRAS mutation subtypes (A) in all patients, (B) in smokers, and (C) in never smokers.
Figure 3
Figure 3
Overall survival (A) according to KRAS mutations and (B) according to KRAS transition versus transversion.
Figure 4
Figure 4
Progression-free survival on first-line chemotherapy (A) according to KRAS mutations and (B) according to KRAS transition versus transversion mutation.

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