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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9858515 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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