No Benefit of Adding Gefitinib to Platinum-Based Doublet in EGFR-Mutant NSCLC After Progression on First-Line Gefitinib
In a phase III IMPRESS trial reported in The Lancet Oncology, Soria et al found no progression-free survival benefit of adding gefitinib (Iressa) to platinum-based doublet chemotherapy in patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC) who had acquired resistance to first-line gefitinib.
Study Details
In the double-blind trial, 265 chemotherapy-naive patients from 11 countries who had stage IIIB to IV EGFR-mutant disease and disease control with first-line gefitinib and recent disease progression took part. They were randomly assigned between March 2012 and December 2013 to receive cisplatin 75 mg/m2 plus pemetrexed (Alimta) 500 mg/m2 on the first day of a maximum of six chemotherapy cycles plus either daily gefitinib 250 mg (n = 133) or placebo (n = 132) continued until disease progression or discontinuation for other reasons.
The primary endpoint was progression-free survival in the intent-to-treat population. The gefitinib and placebo groups were generally balanced for baseline characteristics, including age (median 60 and 58 years), sex (65% and 64% female), country (China for 45% and 44%), and smoking status (never for 66% and 69%).
Progression-Free Survival
Median follow-up was 11.2 months. At the time of data cutoff, progression had occurred in 74% of gefitinib patients and 81% of placebo patients (hazard ratio = 0.86, P = .27). Median progression-free survival was 5.4 months (95% confidence interval [CI] = 4.5–5.7 months) in the gefitinib group vs 5.4 months (95% CI = 4.6–5.5 months) in the placebo group. Follow-up continues for analysis of overall survival.
Adverse Events
The most common adverse events of any grade were nausea (64% in the gefitinib group vs 61% in the placebo group) and decreased appetite (49% vs 34%). The most common grade ≥ 3 adverse events were anemia (8% vs 4%) and neutropenia (7% vs 5%). Serious adverse events occurred in 28% vs 21% of patients.
The investigators concluded: “Continuation of gefitinib after radiological disease progression on first-line gefitinib did not prolong progression-free survival in patients who received platinum-based doublet chemotherapy as subsequent line of treatment. Platinum-based doublet chemotherapy remains the standard of care in this setting.”
Tony S. K. Mok, MD, of The Chinese University of Hong Kong, is the corresponding author of The Lancet Oncology article.
The study was funded by AstraZeneca. For full disclosures of the study authors, visit www.thelancet.com.
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