Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer-Data from Daily Practice

Magdalena Knetki-Wróblewska; Sylwia Tabor; Adam Płużański; Zofia Lewandowska; Andrzej Tysarowski; Hubert Pawlik; Dariusz M Kowalski; Maciej Krzakowski

doi:10.3390/curroncol30010037

Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer-Data from Daily Practice

Curr Oncol. 2022 Dec 29;30(1):462-475. doi: 10.3390/curroncol30010037.

Authors

Magdalena Knetki-Wróblewska¹, Sylwia Tabor¹, Adam Płużański¹, Zofia Lewandowska¹, Andrzej Tysarowski², Hubert Pawlik³, Dariusz M Kowalski¹, Maciej Krzakowski¹

Affiliations

¹ Department of Lung Cancer and Thoracic Tumours, The Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
² Cancer Molecular and Genetic Diagnostics Department, The Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
³ Computational Oncology Department, The Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.

Abstract

Background The implementation of next-generation sequencing (NGS) into daily practice allows for the identification of a greater number of molecular abnormalities. We aimed to confirm the benefits of immunotherapy in the group of patients with KRAS aberrations treated within clinical practice. Methods This study was a retrospective analysis of the patients (pts) treated in routine practice within the National Drug Programme in Poland. The NGS was performed using a FusionPlex Comprehensive Thyroid and Lung (CTL) kit (ArcherDx) and sequenced using a MiniSeq (Illumina). The analyses were performed with the R language environment, version 4.1.3. Results A total of 96 pts with chemotherapy-pre-treated advanced NSCLC (CS III−IV) were qualified for nivolumab or atezolizumab treatment following a molecular diagnosis by the NGS and the exclusion of EGFR and ALK gene abnormalities. A mutation in the KRAS gene was found in 26 patients (27%); among them, the variant p.Gly12Cyc (G12C) was the most common (42%). The median PFS and OS for the overall population were 2 months (95% CI: 1.8−2.75) and 10 months (95% CI: 6.9−16.2), respectively. No differences were observed in terms of the mPFS between the KRAS-mutated and KRAS wild-type (WT) patients. A trend toward a longer OS was observed in the group of patients with the KRAS mutation, but the difference was not statistically significant (p = 0.43). In the multivariate analysis, the presence of mutations in the KRAS gene had no prognostic significance, while the occurence of grade 3 toxicity and the neutrophil-to-lymphocyte ratio (NLR) > 3.5 were found as statistically significant factors. Conclusions Immunotherapy in the second-line treatment of advanced NSCLC allows for a benefit regardless of the KRAS gene mutation status. The treatment sequence, including molecularly targeted drugs such as sotorasib and adagrasib, is still discussed. The NGS is a valuable method to identify a variety of molecular abnormalities in patients with NSCLC in daily practice.

Keywords: KRAS gene; NSCLC; atezolizumab; immunotherapy; nivolumab.

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Humans
Immunotherapy
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Proto-Oncogene Proteins p21(ras) / genetics
Proto-Oncogene Proteins p21(ras) / therapeutic use
Retrospective Studies

Substances

Proto-Oncogene Proteins p21(ras)
KRAS protein, human

Grants and funding

This research received no external funding.