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Neoadjuvant chemoimmunotherapy achieved a pathologic complete response in stage IIIA lung adenocarcinoma harboring RET fusion: a case report.

ABSTRACT: Neoadjuvant chemoimmunotherapy has demonstrated significant benefit for resectable non-small-cell lung cancer (NSCLC) excluding known EGFR/ALK genetic alterations. Recent evidence has shown that neoadjuvant chemoimmunotherapy could be clinically valuable in resectable localized driver gene-mutant NSCLC, though the data still lack robust support, especially for rare oncogenic mutations. Here, we report a patient with stage IIIA lung adenocarcinoma with a RET fusion gene and high expression of PD-L1 who underwent neoadjuvant chemoimmunotherapy and successfully attained a pathologic complete response. The patient has survived for 12 months with no recurrence or metastases after surgery. Our case suggests that this treatment strategy may be an alternative therapeutic option for resectable RET fusion-positive NSCLC patients.

SUBMITTER: Dai M

PROVIDER: S-EPMC10791793 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Neoadjuvant chemoimmunotherapy achieved a pathologic complete response in stage IIIA lung adenocarcinoma harboring RET fusion: a case report.

Dai Minqian M Wang Na N Xia Qin Q Liao Yongde Y Cao Wei W Fan Jun J Zhou Diwei D Wang Sihua S Nie Xiu X

Frontiers in immunology 20240103

Neoadjuvant chemoimmunotherapy has demonstrated significant benefit for resectable non-small-cell lung cancer (NSCLC) excluding known EGFR/ALK genetic alterations. Recent evidence has shown that neoadjuvant chemoimmunotherapy could be clinically valuable in resectable localized driver gene-mutant NSCLC, though the data still lack robust support, especially for rare oncogenic mutations. Here, we report a patient with stage IIIA lung adenocarcinoma with a RET fusion gene and high exp ...[more]

PMID: 38235141

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Neoadjuvant chemoimmunotherapy in resectable stage IIIA/IIIB non-small cell lung cancer.

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| S-EPMC8182703 | biostudies-literature

Case report: Major pathologic response induced by neoadjuvant treatment using BRAF and MEK inhibitors in a patient with stage IIIA lung adenocarcinoma harboring BRAF V600E-mutation.

Project description:Targeted therapy has achieved great success in advanced non-small lung cancer (NSCLC) with driver genes, and neoadjuvant-targeted therapy is increasingly being investigated. Although neoadjuvant-targeted therapy with EGFR-TKI and ALK-TKI showed good efficacy, there is no report of neoadjuvant-targeted therapy to BRAF V600E mutation on NSCLC so far. Here, we report the first case of a successful neoadjuvant-targeted therapy with BRAF and MEK inhibitors followed by radical surgical excision with major pathologic response (MPR) in a patient with stage IIIA lung adenocarcinoma (LUAD) harboring BRAF V600E mutation. The case informs us that targeted therapy with BRAF and MEK inhibitors could be administrated as a neoadjuvant strategy for selected cases of NSCLC harboring BRAF V600E mutation.

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Neoadjuvant Savolitinib targeted therapy stage IIIA-N2 primary lung adenocarcinoma harboring MET Exon 14 skipping mutation: A case report.

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Major pathologic response predicts survival in resectable stage IIIA non-small cell lung cancer after neoadjuvant therapy.

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Case Report: Complete pathologic response to neoadjuvant selpercatinib in a patient with resectable early-stage RET fusion-positive non-small cell lung cancer.

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Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma.

Project description:RET fusions have been found in lung adenocarcinoma, of which KIF5B-RET is the most prevalent. We established inducible KIF5B-RET transgenic mice and KIF5B-RET-dependent cell lines for preclinical modeling of KIF5B-RET-associated lung adenocarcinoma. Doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET transgenic mice developed invasive lung adenocarcinoma with desmoplastic reaction. Tumors regressed upon suppression of KIF5B-RET expression. By culturing KIF5B-RET-dependent BaF3 (B/KR) cells with increasing concentrations of cabozantinib or vandetanib, we identified cabozantinib-resistant RETV804L mutation and vandetanib-resistant-RETG810A mutation. Among cabozantinib, lenvatinib, ponatinib, and vandetanib, ponatinib was identified as the most potent inhibitor against KIF5B-RET and its drug-resistant mutants. Interestingly, the vandetanib-resistant KIF5B-RETG810A mutant displayed gain-of-sensitivity (GOS) to ponatinib and lenvatinib. Treatment of doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET bitransgenic mice with ponatinib effectively induced tumor regression. These results indicate that KIF5B-RET-associated lung tumors are addicted to the fusion oncogene and ponatinib is the most effective inhibitor for targeting KIF5B-RET in lung adenocarcinoma. Moreover, this study finds a novel vandetanib-resistant RETG810A mutation and identifies lenvatinib and ponatinib as the secondary drugs to overcome this vandetanib resistance mechanism. Mol Cancer Ther; 15(10); 2521-9. ©2016 AACR.

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Real-world outcomes of chemoimmunotherapy and selective RET inhibitors in Chinese patients with RET fusion-positive non-small cell lung cancer.

Project description:BackgroundRearranged during transfection (RET) gene fusion is a target for non-small cell lung cancer (NSCLC) treatment, and RET inhibitors are approved for advanced NSCLC. The role of immune checkpoint inhibitors (ICIs) in RET fusion-positive NSCLC remains controversial. This retrospective study analyzed the efficacy of ICIs and RET inhibitors in Chinese patients with RET fusion-positive NSCLC.MethodsData from patients diagnosed with advanced NSCLC harboring RET fusion from Jan 2017 to Sep 2021 were analyzed. Clinicopathological characteristics and outcomes of ICIs and RET inhibitors treatments were collected.ResultsSeventy-five patients with RET fusion-positive advanced NSCLC were identified. The median age of patients was 57 years, half of the patients were female (50.3%), and most were non-smokers or light smokers (72%). Of the cancer types diagnosed in study patients, the KIF5B-RET fusion subtype accounted for 73.3% (55/75), twelve patients (16%) had CCDC6-RET fusion, and three (4%) had NCOA4-RET fusion. Sixteen patients were treated with ICIs. In previously untreated patients, we observed an objective response rate (ORR) of 71.4% and median progression free survival (PFS) of 7.5 months in seven assessable patients. Of four patients with PD-L1 overexpression (>50%) one received pembrolizumab and the other three patients received pemetrexed, carboplatin, and pembrolizumab or camrelizumab. In these patients, the ORR was 75% and disease control rate was 100%. Fifteen patients received selective RET inhibitors (pralsetinib and selpercatinib), resulting in an ORR of 53.3% (8/15) and median PFS of 10.0 months (95% CI 5.2-14.9).ConclusionsICIs for PD-L overexpression and treatment naive patients offer comparable benefits for RET fusion-positive NSCLC, warranting further investigation.

| S-EPMC10831772 | biostudies-literature

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| S-EPMC10236616 | biostudies-literature

Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy.

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| S-EPMC9401519 | biostudies-literature