Analysis of Outcomes in Resected Early-stage NSCLC with Rare Targetable Driver Mutations

Overview

Journal Ther Adv Med Oncol

Specialty Oncology

Date 2024 Dec 30

PMID 39734710

Authors

Nadia Ghazali

Jamie Feng

Katrina Hueniken

Khaleeq Khan

Karmugi Balaratnam

Thomas K Waddell

Kazuhiro Yasufuku

Andrew Pierre

Laura Donahoe

Elliot Wakeam

Marcelo Cypel

Jonathan Yeung

Shaf Keshavjee

Marc de Perrot

Natasha B Leighl

Geoffrey Liu

Penelope A Bradbury

Adrian Sacher

Lawson Eng

Tracy Stockley

Ming Sound Tsao

Frances A Shepherd

Affiliations

Soon will be listed here.

Abstract

Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial.

Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations.

Methods: This retrospective single-center study identified stage I-III NSCLC patients with rare targetable mutations who underwent curative surgery. Tissue-based molecular profiling identified mutations in G12C, Exon20, Erb-B2 receptor tyrosine kinase 2 (), , , B-Raf proto-oncogene () V600E, mesenchymal-epithelial transition factor () exon14 skipping, and rearranged during transfection (). Baseline patient and tumor characteristics, mutation subtype, and co-mutation were correlated with RFS and OS using Cox regression. The G12C cohort was used as the reference for survival comparisons.

Results: Among 225 patients, mutations included the following: G12C ( = 101, 45%), exon 14 skipping ( = 26, 12%), Exon 20 ( = 25, 11%), ( = 25, 11%), fusion ( = 16, 7%), fusion ( = 14, 6%), V600E mutation ( = 13, 6%), and fusion ( = 5, 2%). Five-year survival probabilities were 76% for stage I, 60% for stage II, and 58% for stage III. RFS was shorter across most mutation subgroups compared to G12C, with mutations showing significantly poorer RFS (HR 2.70, = 0.019). By contrast, all mutation subgroups were associated with better OS than G12C. The incidence of brain metastasis was highest in (22% at 5 years). TP53 co-mutation was associated with significantly worse OS (HR 2.35, = 0.008).

Conclusion: While RFS was poorer for most mutations compared to G12C, OS generally was better, suggesting a potential role for postoperative targeted therapies. These findings warrant further investigation through prospective studies and clinical trials to optimize adjuvant treatment strategies for patients with early-stage NSCLC harboring rare driver mutations.

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