Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveal

Authors

Brian De
Ahsan S Farooqi
Kyle G Mitchell
Ethan B Ludmir
Jeff Lewis
Waree Rinsurongkawong
Vadeerat Rinsurongkawong
J Jack Lee
Stephen G Swisher
Don L Gibbons
Jianjun Zhang
Xiuning Le
Yasir Y Elamin
Daniel R Gomez
Matthew S Ning
Steven H Lin
Zhongxing Liao
Joe Y Chang
Ara A Vaporciyan
John V Heymach
Mara B Antonoff
Saumil J Gandhi

Publication Date

1-1-2023

Journal

JCO Precision Oncology

Abstract

Purpose: Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients.

Methods: We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis.

Results: Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. TP53 mutations were identified in 40 of 78 (55%), KRAS in 32 of 95 (34%), EGFR in 24 of 109 (22%), and STK11 in nine of 77 (12%). At median follow-up of 96 months, median OS and PFS were 26 (95% CI, 23 to 31) months and 11 (95% CI, 9 to 13) months, respectively. On multivariable analysis, patients with EGFR mutations had lower mortality risk (hazard ratio [HR], 0.53; 95% CI, 0.29 to 0.98; P = .044) compared with wild-type patients, and patients with STK11 mutations had higher risk of progression or mortality (HR, 2.32; 95% CI, 1.12 to 4.79; P = .023) compared with wild-type patients. TP53 and KRAS mutations were not associated with OS or PFS. Among 71 patients with known EGFR mutational status who received comprehensive LCT, EGFR mutations were associated with lower mortality compared with wild-type (HR, 0.45; 95% CI, 0.22 to 0.94; P = .032).

Conclusion: When compared with wild-type patients, those with EGFR and STK11 mutations had longer OS and shorter PFS, respectively. EGFR mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Benchmarking, Proto-Oncogene Proteins p21(ras), Mutation, ErbB Receptors

DOI

10.1200/PO.22.00540

PMID

36716413

PMCID

PMC9928880

PubMedCentral® Posted Date

1-30-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes