Clinical outcomes of patients with resected, early-stage ALK-positive lung cancer

Abstract

Objectives: Reports of the prognostic significance of ALK-rearrangement in resected non-small cell lung cancer (NSCLC) have been contradictory. We aimed to determine the prognosis of early-stage ALK-positive lung cancers relative to KRAS- and EGFR-mutant lung cancers.

Material and methods: We reviewed medical records of patients with resected NSCLC harboring an ALK rearrangement (n = 29) or a driver mutation in EGFR (n = 255) or KRAS (n = 480). Recurrence-free survival (RFS) was estimated for each genotype with the differences reported as a hazard ratio (HR).

Results: Among the 764 patients, 555 (73%), 101 (13%), and 108 (14%) had stage I, II, and III NSCLC, respectively. ALK-positive patients were distributed across all stages: 10 (34%) stage I, 6 (21%) stage II, and 13 (45%) stage III. Median RFS was not reached for EGFR-mutant patients, 24.3 months (95%CI 11.4-65.3) for ALK-positive patients, and 72.9 months (95%CI 59.7 to undefined) for KRAS-mutant patients. When adjusted for stage, ALK-positive NSCLC remained associated with worse RFS compared to EGFR-mutant (HR 1.8, 95%CI: 1.1-3.1), but not when compared to KRAS-mutant (HR 1.3, 95%CI: 0.8-2.1) NSCLC.

Conclusions: In this large series of resected NSCLC, ALK rearrangements were associated with a trend toward inferior disease outcomes compared to other clinically relevant genomic subsets. These data support the need for clinical trials evaluating use of ALK inhibitors among ALK-positive patients with localized or locally-advanced disease.

Keywords: ALK-rearrangement; Early-stage non-small cell lung cancer.

Conflict of interest statement

Conflicts of Interest

JEC has served as a compensated consultant or received honoraria from Bristol Myers Squibb, AstraZeneca, Genentech, and Merck. IDJ has served as a compensated consultant or received honoraria from Boehringer-Ingelheim and Foundation Medicine. ATS has served as a compensated consultant or received honoraria from Pfizer, Novartis, Genentech/Roche, Ariad/Takeda, Loxo, Blueprint, Foundation Medicine, Ignyta, and KSQ Therapeutics. JFG has served as a compensated consultant or received honoraria from Pfizer, Genentech/Roche, Novartis, Bristol-Myers Squibb, Merck, Incyte, Ariad, Loxo, and Clovis Oncology. The remaining authors have nothing to disclose.

Copyright © 2018 Elsevier B.V. All rights reserved.

Figures

Figure 1

Recurrence free survival by genotype when patients treated with an adjuvant EGFR tyrosine kinase inhibitor were excluded. (A) Stages I and II. (B) Stage III.