Researchers from Asia have reported that first-line treatment with Iressa® (gefitinib) improves progression-free survival over combination treatment with Paraplatin® (carboplatin) and Taxol® (paclitaxel) in advanced non–small cell lung cancer (NSCLC) among nonsmokers and former light smokers in East Asia, according to the results of a study published in the New England Journal of Medicine.

Oral Iressa is approved in the United States as a single-agent treatment for patients with advanced NSCLC who have failed platinum- and taxane-based treatment. Iressa is a selective inhibitor of EGFR-tyrosine kinase. Epidermal growth factor receptor is expressed, overexpressed, or dysregulated in many human solid tumors, including NSCLC. Activation of this receptor is believed to promote tumor growth by blocking apoptosis and by increasing cell proliferation, adhesion and invasive capacity, and motility. Responsive lung tumors are likely to be adenocarcinomas or bronchio-alveolar carcinomas and occur more frequently in non-smokers and women. Responses also occur more frequently in patients with specific mutations of EGFR.

This Phase III multicenter study involved 1,217 patients from China, Taiwan, and Japan who were nonsmokers or former light smokers and had previously untreated advanced (Stage IIIB or IV) NSCLC. The patients were randomly assigned to receive Iressa or Paraplatin/Taxol. The median progression-free survival was 5.7 months in the Iressa group and 5.8 months in the Paraplatin/Taxol group. The 12-month rate of progression-free survival was 24.9% with Iressa and 6.7% with Paraplatin/Taxol. The objective response rate was 43% in the Iressa group compared with 32.2% in the Paraplatin/Taxol group.

Out of the total study group of 1,217 patients, EGFR data was evaluated for 437 patients; 261 patients tested positive for an EFGR mutation. In this subgroup of 261 patients, progression-free survival was significantly longer among those receiving Iressa compared with those receiving Paraplatin/Taxol (HR=0.48). Conversely, in the 176 patients who were EGFR-negative, progression-free survival was significantly longer in the group of patients receiving Paraplatin/Taxol compared with those receiving Iressa (HR=2.85). In the mutation-positive subgroup, the objective response rate was 71.2% with Iressa and 47.3% with Paraplatin/Taxol. In the mutation-negative subgroup, the objective response rate was 1.1% with Iressa and 23.5% with Paraplatin/Taxol.

Iressa was associated with less severe side effects, and patients receiving it reported a better quality of life than those receiving Paraplatin/Taxol. The most common side effects in the Iressa group were rash, acne, and diarrhea, whereas the most common side effects in the Paraplatin/Taxol group were neurotoxicity, low blood counts, and hair loss.

Comments: These researchers concluded that Iressa is superior to Paraplatin/Taxol as first-line treatment for advanced NSCLC in this population. An EGFR-positive tumor is a strong predictor for a better outcome with Iressa. These data strongly suggest that Iressa should not be given to patients who do not have tumors positive for EGFR.

Reference: Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. New England Journal of Medicine [early online publication]. August 19, 2009.