Format

Send to

Choose Destination
J Thorac Oncol. 2019 Jul;14(7):1233-1243. doi: 10.1016/j.jtho.2019.03.007. Epub 2019 Mar 20.

Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non-Small Cell Lung Cancer in the Global Phase III ALEX Study.

Author information

1
Division of Medical Oncology, University of Colorado, Denver, Colorado.
2
Medical University of Gdańsk, Gdańsk, Poland.
3
Lausanne University Hospital, Lausanne, Switzerland.
4
State Key Laboratory of South China, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
5
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
6
University of Michigan, Ann Arbor, Michigan.
7
University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
8
Royal North Shore Hospital, Sydney University, Sydney, Australia.
9
European Institute of Oncology, Scientific Institute for Research and Healthcare, Milan, Italy.
10
Severence Hospital, Seoul, Republic of Korea.
11
Sun Yet-sen University Cancer Center, Guangdong, People's Republic of China.
12
Grenoble University Hospital Center, La Tronche, France.
13
Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Electronic address: Ashaw1@partners.org.

Erratum in

Abstract

INTRODUCTION:

At the prior data cutoff (February 9, 2017) the ALEX trial showed superior investigator-assessed progression-free survival (PFS) for alectinib versus crizotinib in untreated, anaplastic lymphoma kinase (ALK)-positive, advanced NSCLC (hazard ratio = 0.47, 95% confidence interval: 0.34-0.65, p < 0.001). The median PFS in the alectinib arm was not reached versus 11.1 months with crizotinib. Retrospective analyses suggest that the echinoderm microtubule-associated protein-like 4 gene-ALK variant (EML4-ALK) may influence ALK-inhibitor treatment benefit. We present updated analyses, including exploratory subgroup analysis by EML4-ALK variant, after an additional 10 months' follow-up (cutoff December 1, 2017).

METHODS:

Patients were randomized to receive twice-daily alectinib, 600 mg, or crizotinib, 250 mg, until disease progression, toxicity, death, or withdrawal. PFS was determined by the investigators. Baseline plasma and tissue biomarker samples were analyzed by using hybrid-capture, next-generation sequencing to determine EML4-ALK variant.

RESULTS:

Baseline characteristics were balanced. Investigator-assessed PFS was prolonged with alectinib (stratified hazard ratio = 0.43, 95% confidence interval: 0.32-0.58). The median PFS times were 34.8 months with alectinib and 10.9 months with crizotinib. EML4-ALK fusions were detectable in 129 patient plasma samples and 124 tissue samples; variants 1, 2, and 3/ab did not affect PFS, objective response rate, or duration of response. Investigator-assessed PFS was longer for alectinib than for crizotinib across EML4-ALK variants 1, 2, and 3a/b in plasma and tissue. Despite longer treatment duration (27.0 months in the case of alectinib versus 10.8 months in the case of crizotinib), the safety of alectinib compared favorably with that of crizotinib.

CONCLUSION:

Alectinib continues to demonstrate superior investigator-assessed PFS versus crizotinib in untreated ALK-positive NSCLC, irrespective of EML4-ALK variant.

KEYWORDS:

ALEX; Alectinib; EML4-ALK; NGS; Non–small cell lung cancer

PMID:
30902613
DOI:
10.1016/j.jtho.2019.03.007
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center