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

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. Metho...

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Autores principales: Knetki-Wróblewska, Magdalena, Tabor, Sylwia, Płużański, Adam, Lewandowska, Zofia, Tysarowski, Andrzej, Pawlik, Hubert, Kowalski, Dariusz M., Krzakowski, Maciej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9858515/
https://www.ncbi.nlm.nih.gov/pubmed/36661686
http://dx.doi.org/10.3390/curroncol30010037
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author Knetki-Wróblewska, Magdalena
Tabor, Sylwia
Płużański, Adam
Lewandowska, Zofia
Tysarowski, Andrzej
Pawlik, Hubert
Kowalski, Dariusz M.
Krzakowski, Maciej
author_facet Knetki-Wróblewska, Magdalena
Tabor, Sylwia
Płużański, Adam
Lewandowska, Zofia
Tysarowski, Andrzej
Pawlik, Hubert
Kowalski, Dariusz M.
Krzakowski, Maciej
author_sort Knetki-Wróblewska, Magdalena
collection PubMed
description 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.
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spelling pubmed-98585152023-01-21 Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer—Data from Daily Practice Knetki-Wróblewska, Magdalena Tabor, Sylwia Płużański, Adam Lewandowska, Zofia Tysarowski, Andrzej Pawlik, Hubert Kowalski, Dariusz M. Krzakowski, Maciej Curr Oncol Article 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. MDPI 2022-12-29 /pmc/articles/PMC9858515/ /pubmed/36661686 http://dx.doi.org/10.3390/curroncol30010037 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Knetki-Wróblewska, Magdalena
Tabor, Sylwia
Płużański, Adam
Lewandowska, Zofia
Tysarowski, Andrzej
Pawlik, Hubert
Kowalski, Dariusz M.
Krzakowski, Maciej
Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer—Data from Daily Practice
title Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer—Data from Daily Practice
title_full Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer—Data from Daily Practice
title_fullStr Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer—Data from Daily Practice
title_full_unstemmed Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer—Data from Daily Practice
title_short Efficacy of Immunotherapy in Second-Line Treatment of KRAS-Mutated Patients with Non-Small-Cell Lung Cancer—Data from Daily Practice
title_sort efficacy of immunotherapy in second-line treatment of kras-mutated patients with non-small-cell lung cancer—data from daily practice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9858515/
https://www.ncbi.nlm.nih.gov/pubmed/36661686
http://dx.doi.org/10.3390/curroncol30010037
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