Abstract
Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system’s involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669–61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments.
Highlights
Studies have shown that the most altered gene in these cases is MSH2. This is contrary to our study, which did not show that there were alterations in this gene, with the most frequent alteration being in PMS2 [18]
System, and it is possible that in patients with non-small cell lung cancer (NSCLC), this benefit will be demonstrated in the future. This is why, despite the main limitation of the study, which is the low prevalence of mutations in the mismatch repair (MMR) system in NSCLC, the results showed a clear tendency towards a better response to immunotherapy in these patients
Alterations of MMR system genes in NSCLC appear to be associated with an increased response to immunotherapy, similar to other solid tumors
Summary
Immunotherapy has revolutionized the treatment of solid tumors, especially since the introduction of ipilimumab, the first drug approved by the Food and Drug. Administration (FDA) in 2011 for the treatment of advanced unresectable melanoma [1]. Immune checkpoint inhibitors (ICIs) have increased survival rates for non-small cell lung cancer (NSCLC) by up to 20–30% to five years, where previously the overall survival rates (OS) did not reach beyond 12–18 months [2]. One of the current challenges in oncology is the search for patients with long responses to immunotherapy, which would. Biomedicines 2022, 10, 360 allow for precision medicine and higher numbers of long-term survivors. The discovery of different predictive biomarkers that respond to ICIs will revolutionize precision medicine
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