In a phase 2 clinical trial reported in the Journal of Clinical Oncology, Pennell et al found that adjuvant erlotinib improved disease-free survival over historical controls in patients with resected EGFR-mutant NSCLC.
In this study , one hundred patients with resected stage IA to IIIA disease (7th edition of the American Joint Committee on Cancer staging system) who were enrolled at 7 U.S. sites between January 2008 and May 2012. These patients were treated with erlotinib at 150 mg daily for 2 years after standard adjuvant chemotherapy with or without radiotherapy.
The study was powered to demonstrate a primary endpoint of 2-year DFS 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.
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 DFS and OS were not reached; at 5 years, DFS was 56% and OS was 86%.
Of the 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.
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).
Elev1en patients discontinued erlotinib within the first month of treatment due to intolerance. Overall, 40% required a dose reduction to 100 mg/d and 16% to 50 mg/d.