SELECT Trial: Adjuvant Erlotinib in Resected EGFR-Mutant NSCLC
In a phase II trial reported in the Journal of Clinical Oncology, Pennell et al found that adjuvant erlotinib (Tarceva) improved disease-free survival over historical controls in patients with resected EGFR-mutant non–small cell lung cancer (NSCLC).
In the study, 100 patients with resected stage IA to IIIA disease (7th edition of the American Joint Committee on Cancer staging system) were enrolled at 7 U.S. sites between January 2008 and May 2012. These patients were treated with erlotinib at 150 mg/d for 2 years after standard adjuvant chemotherapy with or without radiotherapy.
The study was powered to demonstrate a primary endpoint of 2-year disease-free survival greater than 85%, improving on the rate of 76% observed in genotype-matched historic controls. Overall, 13% of patients had stage IA disease; 32%, stage IB; 11%, stage IIA; 16%, stage IIB; and 28%, stage IIIA.
Disease-Free Survival
A total of 69% of patients completed the 2-year course. Median follow-up was 5.2 years. Disease-free survival at 2 years was 88% among all patients (P = .0047 vs historical controls), including 96% with stage I disease, 78% with stage II disease, and 91% with stage III disease. Median disease-free and overall survival were not reached; at 5 years, disease-free survival was 56% and overall survival was 86%.
Of 40 patients with disease recurrence, 4 had recurrence during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of 24 patients with recurrence who underwent additional biopsy, T790M resistance mutation was detected in 1 patient. A total of 26 patients with recurrence received retreatment with erlotinib for a median of 13 months.
Adverse Events
The investigators noted that toxicities were typical of erlotinib, with the most common adverse events of any grade considered related to treatment being rash (74%), diarrhea (71%), dry skin (48%), fatigue (46%), nausea/vomiting (33%), nail changes (27%), pruritus (23%), stomatitis (20%), and transaminitis (15%). The most common grade 3 adverse events considered related to treatment were rash (13%) and diarrhea (3%). There were no grade 4 or 5 adverse events. Pulmonary fibrosis occurred in 1 patient (grade 2).
Eleven patients discontinued erlotinib within the first month of treatment due to intolerance. Overall, 40% required dose reduction to 100 mg/d and 16% to 50 mg/d.
The investigators concluded, “Patients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year [disease-free survival] compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.”
Nathan A. Pennell, MD, PhD, of the Cleveland Clinic Taussig Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was an investigator-initiated trial funded by Genentech. The study authors’ full disclosures may be found at jco.ascopubs.org.
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