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- Title
Real‐world retrospective study of KRAS mutations in advanced non–small cell lung cancer in the era of immunotherapy.
- Authors
Bironzo, Paolo; Cani, Massimiliano; Jacobs, Francesca; Napoli, Valerio M.; Listì, Angela; Passiglia, Francesco; Righi, Luisella; Di Maio, Massimo; Novello, Silvia; Scagliotti, Giorgio V.
- Abstract
Background: KRAS mutation‐positive (KRAS‐positive), advanced nonsmall‐cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are extremely heterogeneous from a biologic point of view, and real‐world data by mutation subtype in the era of immunotherapy are still incomplete. Methods: The objective of this study was to retrospectively analyze all consecutive patients with advanced/metastatic, KRAS‐positive NSCLC who were diagnosed at a single academic institution since the advent of immunotherapy. The authors report on the natural history of the disease as well as the efficacy of first‐line treatments in the entire cohort and by KRAS mutation subtypes as well as the presence/absence of co‐mutations. Results: From March 2016 to December 2021, the authors identified 199 consecutive patients who had KRAS‐positive, advanced or metastatic NSCLC. The median overall survival (OS) was 10.7 months (95% confidence interval [CI], 8.5–12.9 months), and there were no differences by mutation subtype. Among 134 patients who received first‐line treatment, the median OS was 12.2 months (95% CI, 8.3–16.1 months), and the median progression‐free survival was 5.6 months (95% CI, 4.5–6.6 months). At multivariate analysis, only an Eastern Cooperative Oncology Group performance status of 2 was associated with significantly shorter progression‐free survival and OS. Conclusions: KRAS‐positive, advanced NSCLC is characterized by a poor prognosis despite the introduction of immunotherapy. Survival was not associated with KRAS mutation subtype. Plain Language Summary: This study evaluated the efficacy of systemic therapies for advanced/metastatic nonsmall cell lung cancer harboring KRAS mutations, along with the potential predictive and prognostic role of mutation subtypes. The authors found that advanced/metastatic, KRAS‐positive nonsmall cell lung cancer is characterized by a poor prognosis and that first‐line treatment efficacy is not related to different KRAS mutations, although a numerically shorter median progression‐free survival was observed in patients who had p.G12D and p.G12A mutations.These results underline the need for novel treatment options in this population, such as next‐generation KRAS inhibitors, which are in clinical and preclinical development. Despite the introduction of immunotherapy, KRAS‐positive, advanced non–small cell lung cancer is still characterized by a poor prognosis. In this study, KRAS mutation subtypes did not influence survival.
- Subjects
NON-small-cell lung carcinoma; RAS oncogenes; PROGRESSION-free survival; IMMUNOTHERAPY; GENETIC mutation
- Publication
Cancer (0008543X), 2023, Vol 129, Issue 11, p1662
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.34731