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.
- Camidge DR Division of Medical Oncology, University of Colorado, Denver, Colorado.
- Dziadziuszko R Medical University of Gdańsk, Gdańsk, Poland.
- Peters S Lausanne University Hospital, Lausanne, Switzerland.
- Mok T State Key Laboratory of South China, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
- Noe J F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- Nowicka M F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- Gadgeel SM University of Michigan, Ann Arbor, Michigan.
- Cheema P University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.
- Pavlakis N Royal North Shore Hospital, Sydney University, Sydney, Australia.
- de Marinis F European Institute of Oncology, Scientific Institute for Research and Healthcare, Milan, Italy.
- Cho BC Severence Hospital, Seoul, Republic of Korea.
- Zhang L Sun Yet-sen University Cancer Center, Guangdong, People's Republic of China.
- Moro-Sibilot D Grenoble University Hospital Center, La Tronche, France.
- Liu T F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- Bordogna W F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- Balas B F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- Müller B F. Hoffmann-La Roche Ltd, Basel, Switzerland.
- Shaw AT Massachusetts General Hospital Cancer Center, Boston, Massachusetts. Electronic address: Ashaw1@partners.org.
- 2019-03-24
Published in:
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. - 2019
ALEX
Alectinib
EML4-ALK
NGS
Non–small cell lung cancer
Adolescent
Adult
Aged
Anaplastic Lymphoma Kinase
Antineoplastic Combined Chemotherapy Protocols
Brain Neoplasms
Carbazoles
Carcinoma, Non-Small-Cell Lung
Cohort Studies
Crizotinib
Female
Follow-Up Studies
Humans
Lung Neoplasms
Male
Middle Aged
Oncogene Proteins, Fusion
Piperidines
Prognosis
Survival Rate
Young Adult
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1016/j.jtho.2019.03.007
- PMID 30902613
- Persistent URL
- https://folia.unifr.ch/global/documents/186262
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