From bench to bedside and beyond

Jain, Deepali; Gheware, Atish; Rathor, Amber

doi:10.4103/crst.crst_248_21

Cited by 3 publications

(1 citation statement)

References 6 publications

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“…KRAS mutations were first identified in lung cancers more than three decades ago [1][2][3]. There has been a recent resurgence in interest in this subset of patients with lung cancer due to the development of agents targeting KRAS G12C, with promising phase 2 data for sotorasib [4,5] leading to accelerated approval from the United States Food and Drug Administration in patients with locally advanced and metastatic KRAS mutant non-small cell lung cancer (NSCLC) who have progressed on a first-line agent.…”

Section: Introductionmentioning

confidence: 99%

Clinical characteristics, outcomes and prognostic factors in KRAS mutant lung cancers: experience from a tertiary care cancer center in India

Noronha,

Sarkar,

Patil

et al. 2024

ecancer Journal

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Objectives Kirsten rat sarcoma viral oncogene homologue ( KRAS ) mutations in lung cancers, long considered untargetable, have had a recent rise in interest due to promising data of agents targeting KRAS p.G12C. As Indian data are scarce, we sought to identify baseline clinical characteristics, prognostic factors and outcomes of lung cancer patients with KRAS mutations at our hospital. Methods Patients with KRAS mutant lung cancers treated at our institute from 2016 to 2022 were analysed. Results 133 patients with KRAS mutant lung cancers were identified. Median age was 57 (interquartile range 28–78) years, and 58 (43.6%) were smokers. 17 (12.7%) had brain metastases. The commonest variant was p.G12C, seen in 53 (39.8%) patients. Six (4.5%) had programmed death ligand 1 (PDL-1) expression >50% by Ventana SP263 PDL-1 assay, and 13 (9.7%) had epidermal growth factor mutation. Of 92 patients with available treatment details, the majority received intravenous chemotherapy, nine (9.8%) received tyrosine kinase inhibitors and four (4.4%) received immunotherapy (pembrolizumab). Median progression-free survival (PFS) with first-line therapy was 6 (95% confidence interval (CI) 2.8–9.2) months and median overall survival (OS) was 12 (CI 9.2–14.8) months. The incidence of brain metastases was higher in patients with G12C mutations ( p = 0.025). Brain metastases (HR: 3.57, p < 0.001), Eastern Cooperative Oncology Group performance status (PS) ≥ 2 (HR: 2.13, p = 0.002) and G12C mutation (HR: 1.84, p = 0.011) were associated with inferior PFS, while brain metastases (HR: 4.6, p < 0.001), PS ≥ 2 (HR: 2.33, p = 0.001) and G12C mutation (HR: 1.93, p = 0.01) were associated with inferior OS. Conclusion This is the largest dataset of KRAS mutant lung cancers from India. Brain metastases were higher in patients with G12C mutations and associated with poorer PFS and OS. G12C mutation and PS ≥ 2 were also associated with inferior PFS and OS. Experience with targeted therapy for KRAS mutations remains an area of future exploration due to the unavailability of these agents in India.

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