Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations

Dantoing, Edouard; Piton, Nicolas; Salaün, Mathieu; Thiberville, Luc; Guisier, Florian

doi:10.3390/ijms22126288

Cited by 72 publications

(47 citation statements)

References 104 publications

(63 reference statements)

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“…In addition to EGFR mutation, a multi-omics analysis identified that activating mutations in receptor tyrosine kinases (RTK) genes, such as c-MET mutation or amplification, FGFR1 amplification, human EGFR 2 (HER2) point mutation, and insulin-like growth factor 1 receptor (IGF1R) amplification, are associated with primary resistance to ICIs regardless of PD-L1 expression and TMB [ 21 , 89 ]. The activation of Ras/Raf/MEK/ERK signaling also upregulates PD-L1 expression in NSCLC with activated alterations of RTK genes, although IHC of PD-L1 for these genes alterations was not well studied because of the low frequency.…”

Section: The Association Between Pd-l1 Expression and Efficacy Of Icis In Nsclc With Driver Gene Alterationsmentioning

confidence: 99%

Current Immunotherapeutic Strategies Targeting the PD-1/PD-L1 Axis in Non-Small Cell Lung Cancer with Oncogenic Driver Mutations

Tanaka

Morise

2021

IJMS

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Treatment strategies targeting programed cell death 1 (PD-1) or its ligand, PD-L1, have been developed as immunotherapy against tumor progression for various cancer types including non-small cell lung cancer (NSCLC). The recent pivotal clinical trials of immune-checkpoint inhibiters (ICIs) combined with cytotoxic chemotherapy have reshaped therapeutic strategies and established various first-line standard treatments. The therapeutic effects of ICIs in these clinical trials were analyzed according to PD-L1 tumor proportion scores or tumor mutational burden; however, these indicators are insufficient to predict the clinical outcome. Consequently, molecular biological approaches, including multi-omics analyses, have addressed other mechanisms of cancer immune escape and have revealed an association of NSCLC containing specific driver mutations with distinct immune phenotypes. NSCLC has been characterized by driver mutation-defined molecular subsets and the effect of driver mutations on the regulatory mechanism of PD-L1 expression on the tumor itself. In this review, we summarize the results of recent clinical trials of ICIs in advanced NSCLC and the association between driver alterations and distinct immune phenotypes. We further discuss the current clinical issues with a future perspective for the role of precision medicine in NSCLC.

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Section: The Association Between Pd-l1 Expression and Efficacy Of Icis In Nsclc With Driver Gene Alterationsmentioning

confidence: 99%

Current Immunotherapeutic Strategies Targeting the PD-1/PD-L1 Axis in Non-Small Cell Lung Cancer with Oncogenic Driver Mutations

Tanaka

Morise

2021

IJMS

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“…Thus, this oncogenic expedient (69) can be exploited for therapeutic purposes in IPF. Moreover, it has been already reported that, in lung cancer mutations occurring in several oncogenes among which MET, modulate tumor microenvironment and a positive correlation between MET amplification and PDL1 overexpression has been already reported (237,238). Thus, in a context-specific regulation of its expression, MET might become a functional marker of IPF and an actionable target, positively associated to response to ICIs (Figure 2).…”

Section: Rationale For Immunotherapy In Fibrotic Lungmentioning

confidence: 83%

The oncogenic landscape of the idiopathic pulmonary fibrosis: a narrative review

Stella¹,

D’Agnano²,

Piloni³

et al. 2022

Transl Lung Cancer Res

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Background and Objective: Translational research is a source of continuous innovation in medicine, more particularly for clinical research on new treatment modalities in idiopathic pulmonary fibrosis (IPF) patients.However, the heterogeneity of the disease is well recognized, and different pathological and molecular settings have been identified. The molecular mechanisms by which IPF proceeds in time and space remains poorly understood. Although some IPF features are reminiscent of cancer, the dynamics of malignant divergent clonal selective pressure and heterogeneity clearly differ from those occurring in IPF. This is reflected in the absence of patient proper selection and stratification to biological agents (pirfenidone, nintedanib) which limit therapeutic efficacy. Consequently, increased costs are related to the clinical management of advanced IPF patients. Steady collaboration and fluid communication between pneumo-oncologists, radiologists and molecular biologists is a clear priority for the correct interpretation of tests and the definition of effective personalized strategies against this orphan disease. The present work aims at providing the most relevant hints shared by cancer and IPF.Methods: A systematic literature review was performed to identify all relevant data. The examined databases were Scopus, Web of Science, Cochrane, Google Scholar, and PubMed. The last search was run on January 5, 2022. We have primarily conducted separated research for lung cancer, IPF, genetics, epigenetics, surgery in IPF and cancer.

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“…RET gene rearrangements are identified in 1–2% of patients with NSCLC and in some of them, high PD-L1 expression coexists (13–50% of patients in small published cohorts) [ 7 , 15 , 16 ]. High PD-L1 expression is an established positive predictive factor for immunotherapy in the general population.…”

Section: Discussionmentioning

confidence: 99%

“…The value of immunotherapy, such as anti-PD-1/PD-L1 monotherapy in patients with molecular alterations, is questionable. It is considered to be of lower efficacy, especially in patients with EGFR activating mutations and ALK rearrangements [ 4 , 16 , 17 , 18 ]. There are several theories that could explain the low activity of this type of treatment.…”

Section: Discussionmentioning

confidence: 99%

Non-Small-Cell Lung Cancer Patients with Coexistence of High PD-L1 Expression and RET Fusion—Which Path Should We Follow? Case Reports and Literature Review

Knetki-Wróblewska

Wojas‐Krawczyk

Kowalski

et al. 2022

JCM

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Pembrolizumab is widely used in first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC) with high PD-L1 expression. The activity of pembrolizumab in NSCLC patients with rare molecular alterations is poorly characterised. RET gene rearrangements are identified in 1–2% of lung cancer patients. Here, we present two cases of RET-rearranged NSCLC patients with high PD-L1 expression (>50%), treated with pembrolizumab within routine clinical practice. Pembrolizumab was ineffective in both cases—single-agent immunotherapy seems to be of limited value in this group of patients. Selective RET-inhibitors, if available, are the optimal treatment for patients with RET fusion nowadays. The best sequence of the therapy is still not defined.

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Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations

Cited by 72 publications

References 104 publications

Current Immunotherapeutic Strategies Targeting the PD-1/PD-L1 Axis in Non-Small Cell Lung Cancer with Oncogenic Driver Mutations

Current Immunotherapeutic Strategies Targeting the PD-1/PD-L1 Axis in Non-Small Cell Lung Cancer with Oncogenic Driver Mutations

The oncogenic landscape of the idiopathic pulmonary fibrosis: a narrative review

Non-Small-Cell Lung Cancer Patients with Coexistence of High PD-L1 Expression and RET Fusion—Which Path Should We Follow? Case Reports and Literature Review

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