SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer

Abstract

PURPOSE Given 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 METHODS In this open-label phase II trial, patients with resected stage IA to IIIA (7th 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%. RESULTS Patients (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. CONCLUSION Patients 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.

A CRISPR Test for Rapidly and Sensitively Detecting Circulating EGFR Mutations

“…Second, current ASCO/CAP/IASLC guidelines recommend molecular testing for EGFR mutations, ALK and ROS1 rearrangements, but also for BRAF mutations and exon 14 mutations, HER2 mutations, and RET rearrangements [15]. NGS analysis of tissue and plasma specimen has been shown to be more cost effective than single gene testing in NSCLC [16,17]. For example, a plasma NGS test (Guardant360) could detect guideline-recommended biomarker-positive patients at a rate similar to physician discretion standard-of-care tissue genomic testing [18].…”

Interdisciplinary multimodality management of stage III nonsmall cell lung cancer

“…Therefore, accurate determination of the histologic subtype of lung cancer is mandatory in stage IV. It is not yet clear for stage III [16,17]. In resected pulmonary carcinomas, histology can provide additional prognostic information beyond TNM staging; until now without therapeutic consequences.…”

What can artificial intelligence teach us about the molecular mechanisms underlying disease?

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