First-Line Targeted Treatment Approved for Metastatic NSCLC

Oncologists now have a newly approved first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC). On July 13, 2015, the US Food and Drug Administration (FDA) approved gefitinib (Iressa) for patients whose tumors express the most common types of epidermal growth factor receptor (EGFR) mutations in NSCLC (exon 19 deletions or exon 21 [L858R] substitution gene mutations). The FDA also approved a companion test (therascreen^®EGFR RGQ PCR Kit) to identify appropriate patients.

“Iressa offers another effective first-line therapy option for selected lung cancer patients. This approval provides further support for a highly targeted approach to treating cancer,” said Richard Pazdur, MD, who is the director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, Bethesda, Md.

Gefitinib is an EGFR tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells, and it was granted Orphan Drug Designation by the FDA in August 2014 for the treatment of EGFR mutation-positive NSCLC.

The FDA approval of gefitinib is based on data from the phase IV IFUM (IRESSA Follow-Up Measure) study, which assessed gefitinib as a first-line treatment for 106 Caucasian patients with locally advanced or metastatic EGFR mutation-positive NSCLC. Participants received gefitinib 250 mg once daily. Results showed that tumors shrank in about 50% of patients after treatment and this effect lasted an average of 6 months. The response rates were similar in patients whether their tumors had EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

These results were supported by a retrospective analysis of another clinical trial, IPASS clinical trial (IRESSA Pan-ASia Study), which identified a subgroup of 186 patients with EGFR mutation-positive metastatic NSCLC receiving first-line treatment. Patients were randomized to receive gefitinib or up to six cycles of carboplatin/paclitaxel. The results from this subgroup suggested an improvement in progression-free survival (PFS) with gefitinib compared to carboplatin/paclitaxel.  

The most common side effects with this agent are diarrhea and skin reactions, including rash, acne, dry skin, and pruritus. However, it can cause interstitial lung disease, liver damage, gastrointestinal perforation, and ocular disorders.

Gefitinib originally received accelerated approval in 2003 for the treatment of patients with advanced NSCLC after progression on platinum doublet chemotherapy and docetaxel, but was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit. Monday's announcement is an approval for EGFR mutation-positive, previously untreated metastatic NSCLC--different from the 2003 approval.  

Gefitinib is approved in 91 countries for the treatment of adult patients with locally advanced or metastatic EGFR mutation-positive NSCLC. AstraZeneca, which is marketing gefitinib, is also studying it in combination with other investigational medicines, including the company’s anti-PD-L1 monoclonal antibody, durvalumab (MEDI4736) as a combination treatment for a broader range of lung cancer patients.