FDA Modifies Indication for Erlotinib in NSCLC

The use is limited to patients whose tumours have specific EGFR mutations

On 18 October, 2016, the US Food and Drug Administration (FDA) modified the indication for erlotinib (TARCEVA, Astellas Pharm Global Development Inc.) for treatment of non-small cell lung cancer (NSCLC) to limit use to patients whose tumours have specific epidermal growth factor receptor (EGFR) mutations.

The labelling change applies to patients with NSCLC receiving maintenance or second or greater line treatment. These indications will be limited to those patients whose tumours have EGFR exon 19 deletions or exon 21 L858R substitution mutations as detected by an FDA-approved test.

The first-line indication previously was limited to patients with EGFR exon 19 deletions or exon 21 substitution mutations.

This labelling supplement is based on the results of the IUNO trial, a randomised, double-blind, placebo-controlled, trial of erlotinib administered as maintenance therapy in 643 patients with advanced NSCLC who had not experienced disease progression or unacceptable toxicity during four cycles of platinum-based first-line chemotherapy. Patients whose tumours harboured activating EGFR mutations (exon 19 deletions or exon 21 L858R mutations) were excluded from this trial.

Patients were randomised 1:1 to receive erlotinib or placebo orally once daily (322 erlotinib, 321 placebo) until disease progression or unacceptable toxicity. Following progression on initial therapy, patients were eligible to enter an open-label phase. In total, 50% of patients randomised to erlotinib entered the open-label phase and received chemotherapy, while 77% of patients randomised to placebo entered the open-label phase and received erlotinib. 

The trial’s primary endpoint was overall survival. Results demonstrated that survival following treatment with erlotinib was not better than placebo administered as maintenance in patients with metastatic NSCLC tumours not harbouring EGFR-activating mutations. No difference in progression-free survival between the erlotinib arm and the placebo arm was observed.

FDA will not require new post-marketing requirements or request post-marketing commitments based on the results of the IUNO trial.

Full prescribing information is available here.