Poor performance status patient with long-lasting major response to pembrolizumab in advanced non-small-cell lung cancer with coexisting POLE mutation and deficient mismatch repair pathway

Vauchier, Charles; Pluvy, Johan; Théou–Anton, Nathalie; Soussi, Ghassen; Poté, Nicolas; Brosseau, Solenn; Gounant, V.; Zalcman, Gérard

doi:10.1016/j.lungcan.2021.07.016

Cited by 8 publications

(3 citation statements)

References 11 publications

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“…For example, patients with POLE-mutated endometrial cancer had a better response to treatment [82,83]. This association was also found in non-small cell lung cancer [84,85]. Nevertheless, POLE/POLD1 mutations appear not so frequent in NSCLC.…”

Section: The Role Of Mutationsmentioning

confidence: 84%

Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer

Pabst

Lopes

Bertrand

et al. 2023

IJMS

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The therapeutic algorithm of lung cancer has recently been revolutionized by the emergence of immune checkpoint inhibitors. However, an objective and durable response rate remains low with those recent therapies and some patients even experience severe adverse events. Prognostic and predictive biomarkers are therefore needed in order to select patients who will respond. Nowadays, the only validated biomarker is the PD-L1 expression, but its predictive value remains imperfect, and it does not offer any certainty of a sustained response to treatment. With recent progresses in molecular biology, genome sequencing techniques, and the understanding of the immune microenvironment of the tumor and its host, new molecular features have been highlighted. There are evidence in favor of the positive predictive value of the tumor mutational burden, as an example. From the expression of molecular interactions within tumor cells to biomarkers circulating in peripheral blood, many markers have been identified as associated with the response to immunotherapy. In this review, we would like to summarize the latest knowledge about predictive and prognostic biomarkers of immune checkpoint inhibitors efficacy in order to go further in the field of precision immuno-oncology.

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Section: The Role Of Mutationsmentioning

confidence: 84%

Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer

Pabst

Lopes

Bertrand

et al. 2023

IJMS

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“…( 51 ), and Vauchier et al. ( 52 ) reported that patients with MMR mutations and MSI-H achieved durable benefits from ICIs. In Han et al.…”

Section: Discussionmentioning

confidence: 99%

Long-term benefit of immunotherapy in a patient with squamous lung cancer exhibiting mismatch repair deficient/high microsatellite instability/high tumor mutational burden: A case report and literature review

Wan

et al. 2023

Front. Immunol.

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Genetic mutations that render mismatch repair defective may result in microsatellite instability, which is common in colorectal carcinomas and gastric cancers as well as Lynch syndrome. Mismatch repair deficiency/high microsatellite instability (dMMR/MSI-H) predicts the tumor response to immune checkpoint inhibitors. However, few studies have evaluated the efficacy of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) patients with dMMR/MSI-H. In this work, we present a patient with advanced squamous lung cancer with dMMR/MSI-H and a high tumor mutational burden (TMB-H) who obtained a long-term benefit from immunotherapy. NSCLC patients with dMMR/MSI-H/TMB-H may thus benefit from immune checkpoint inhibitors.

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“…Increasing studies have reported that mutated genes carrying single nucleotide variants (SNVs) are significantly related with the ICB response ( 7 , 8 ). For example, STK11 , B2M , and EGFR mutations or MDM2 amplification were associated with poor responsiveness or even hyper-progressive disease (HPD) ( 9 , 10 ), whereas TP53 , KRAS , and POLE mutations or KP (co-mutations of KRAS and TP53 ) molecular sub-type were positively related with ICB response in advanced NSCLC ( 11 , 12 ). Patients with KL (co-mutations of KRAS and STK11 ) showed poor responses ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Deep learning to estimate durable clinical benefit and prognosis from patients with non-small cell lung cancer treated with PD-1/PD-L1 blockade

et al. 2022

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Different biomarkers based on genomics variants have been used to predict the response of patients treated with PD-1/programmed death receptor 1 ligand (PD-L1) blockade. We aimed to use deep-learning algorithm to estimate clinical benefit in patients with non-small-cell lung cancer (NSCLC) before immunotherapy. Peripheral blood samples or tumor tissues of 915 patients from three independent centers were profiled by whole-exome sequencing or next-generation sequencing. Based on convolutional neural network (CNN) and three conventional machine learning (cML) methods, we used multi-panels to train the models for predicting the durable clinical benefit (DCB) and combined them to develop a nomogram model for predicting prognosis. In the three cohorts, the CNN achieved the highest area under the curve of predicting DCB among cML, PD-L1 expression, and tumor mutational burden (area under the curve [AUC] = 0.965, 95% confidence interval [CI]: 0.949–0.978, P< 0.001; AUC =0.965, 95% CI: 0.940–0.989, P< 0.001; AUC = 0.959, 95% CI: 0.942–0.976, P< 0.001, respectively). Patients with CNN-high had longer progression-free survival (PFS) and overall survival (OS) than patients with CNN-low in the three cohorts. Subgroup analysis confirmed the efficient predictive ability of CNN. Combining three cML methods (CNN, SVM, and RF) yielded a robust comprehensive nomogram for predicting PFS and OS in the three cohorts (each P< 0.001). The proposed deep-learning method based on mutational genes revealed the potential value of clinical benefit prediction in patients with NSCLC and provides novel insights for combined machine learning in PD-1/PD-L1 blockade.

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Poor performance status patient with long-lasting major response to pembrolizumab in advanced non-small-cell lung cancer with coexisting POLE mutation and deficient mismatch repair pathway

Cited by 8 publications

References 11 publications

Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer

Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer

Long-term benefit of immunotherapy in a patient with squamous lung cancer exhibiting mismatch repair deficient/high microsatellite instability/high tumor mutational burden: A case report and literature review

Deep learning to estimate durable clinical benefit and prognosis from patients with non-small cell lung cancer treated with PD-1/PD-L1 blockade

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