SELECT: A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small-cell lung cancer Journal Article


Authors: Pennell, N. A.; Neal, J. W.; Chaft, J. E.; Azzoli, C. G.; Jänne, P. A.; Govindan, R.; Evans, T. L.; Costa, D. B.; Wakelee, H. A.; Heist, R. S.; Shapiro, M. A.; Muzikansky, A.; Murthy, S.; Lanuti, M.; Rusch, V. W.; Kris, M. G.; Sequist, L. V.
Article Title: SELECT: A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small-cell lung cancer
Abstract: PurposeGiven the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC.Materials and MethodsIn this open-label phase II trial, patients with resected stage IA to IIIA (7(th) edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%.ResultsPatients (N = 100) were enrolled at seven sites from January 2008 to May 2012; 13% had stage IA disease, 32% had stage IB disease, 11% had stage IIA disease, 16% had stage IIB disease, and 28% had stage IIIA disease. Toxicities were typical of erlotinib; there were no grade 4 or 5 adverse events. Forty percent of patients required erlotinib dose reduction to 100 mg per day and 16% to 50 mg per day. The intended 2-year course was achieved in 69% of patients. The median follow-up was 5.2 years, and 2-year DFS was 88% (96% stage I, 78% stage II, 91% stage III). Median DFS and overall survival have not been reached; 5-year DFS was 56% (95% CI, 45% to 66%), 5-year overall survival was 86% (95% CI, 77% to 92%). Disease recurred in 40 patients, with only four recurrences during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of patients with recurrence who underwent rebiopsy (n = 24; 60%), only one had T790M mutation detected. The majority of patients with recurrence were retreated with erlotinib (n = 26; 65%) for a median duration of 13 months.ConclusionPatients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year DFS compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.
Keywords: placebo; chemotherapy; gastrointestinal stromal tumor; tyrosine kinase inhibitors; tamoxifen; double-blind; efficacy; 1st-line treatment; multicenter; open-label
Journal Title: Journal of Clinical Oncology
Volume: 37
Issue: 2
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2019-01-10
Start Page: 97
End Page: 104
Language: English
ACCESSION: WOS:000456131200002
DOI: 10.1200/jco.18.00131
PROVIDER: wos
PUBMED: 30444685
Notes: Article -- Source: Wos
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MSK Authors
  1. Valerie W Rusch
    638 Rusch
  2. Jamie Erin Chaft
    120 Chaft
  3. Mark Kris
    581 Kris