In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.
On October 18, 2016, the indication for erlotinib (Tarceva) in the treatment of non–small cell lung cancer (NSCLC) was modified to limit use to patients with tumors with specific epidermal growth factor receptor (EGFR) mutations in maintenance or second- or greater-line treatment; these mutations consist of exon 19 deletions or exon 21 L858R substitutions detected by a U.S. Food and Drug Administration (FDA)-approved test.1,2 The first-line indication for erlotinib already had been limited to patients with EGFR exon 19 deletions or exon 21 substitution mutations.
Data Supporting Modification
The labeling modification is based on the lack of efficacy of erlotinib maintenance treatment in patients without EGFR-activating mutations in the double-blind IUNO trial. In the trial, 643 patients who had not experienced disease progression or unacceptable toxicity during 4 cycles of platinum-based first-line chemotherapy were randomized to receive erlotinib at 150 mg (n = 322) or placebo (n = 321) once daily until disease progression or unacceptable toxicity. Following disease progression on initial therapy, patients were eligible to enter an open-label phase; 50% of erlotinib patients entered the open-label phase and received chemotherapy, and 77% of placebo patients entered the open-label phase and received erlotinib.
Patients had a median age of 61 years (35% aged ≥ 65 years); 75% were male; 77% were white and 21%, Asian; Eastern Cooperative Oncology Group performance status was 0 in 28% and 1 in 72%; 16% were never smokers and 58% current smokers; 57% had adenocarcinoma and 35% squamous cell carcinoma; and 22% had stage IIIB disease not amenable to combined-modality treatment and 78% had stage IV disease.
The primary efficacy outcome was overall survival. Median overall survival was 9.7 months in the erlotinib group vs 9.5 months in the placebo group (hazard ratio [HR] = 1.02, 95% confidence interval [CI] = 0.85–1.22). Median progression-free survival was 3.0 vs 2.8 months, respectively (HR = 0.94, 95% CI = 0.80–1.11).
The FDA will not require new postmarketing requirements or request postmarketing commitments based on the results of the IUNO trial. ■
1. U.S. Food and Drug Administration: Erlotinib (Tarceva). Available at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm525739.htm. Accessed October 21, 2016.
2. Tarceva (erlotinib) tablets prescribing information, Astellas Pharma and Genentech, October 2016. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2016/021743s025lbl.pdf. Accessed October 21, 2016.
Health-care professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System by completing a form online at www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).