- Front-line gefitinib in combination with carboplatin and pemetrexed achieves superior PFS and OS vs gefitinib alone in patients with NSCLC featuring endothelial growth factor receptor (EGFR) mutations.
Why this matters
- EGFR-tyrosine kinase inhibitor (TKI) therapy is a standard first-line treatment for advanced NSCLC with EGFR-sensitive mutations.
- EGFR-TKI yields superior PFS compared with chemotherapy, but differences in OS are unclear.
- Phase 2 results have suggested the efficacy of gefitinib, along with carboplatin and pemetrexed.
- This randomized phase 3 trial compared the efficacy of the combination therapy with gefitinib alone on PFS and OS.
- 345 patients (20-75 years old) with previously untreated, stage IIIB, nonsquamous NSCLC positive for EGFR mutation randomly assigned 1:1 to induction with daily gefitinib along with carboplatin+pemetrexed (4-6 cycles, every 21 days; n=170; 2 exclusions) or daily gefitinib (n=172; 1 exclusion), followed by maintenance with daily gefitinib and pemetrexed (every 21 days) or platinum-based regimen, respectively.
- Gefitinib, 250 mg/day; carboplatin area under the curve, 6; pemetrexed, 500 mg/m2
- Treatment continued until progression.
- Primary endpoints: OS, PFS; secondary endpoints: objective response rate, safety, QoL.
- 60-month follow-up.
- Funding: North-East Japan Study group.
- Study groups were balanced at baseline for age, sex, smoking history, Eastern Cooperative Oncology Group Performance Status, clinical stage, and prevalence of adenocarcinoma.
- 60-month PFS: 11.2 (9.0-13.4) months with gefitinib, 20.9 (18.0-24.0) months for combination treatment (HR, 0.494; 95% CI 0.391-0.625; P<.001>
- 60-month OS: 38.8 (31.1-50.8) months with gefitinib, 52.2 (44.0-not applicable) months for combination treatment (HR, 0.695; 95% CI 0.520-0.927; P<.013>
- Overall response rate of 67.4% for gefitinib and 84.9% for combination treatment.
- Neutropenia was more common in the combination group (any grade: 4.1% vs 59.8%; ≥grade 3: 0.6% vs 31.4%), as was anemia (any grade: 20.3% vs 66.9%; ≥grade 3: 2.3% vs 21.3%).
- "Performance status seemed to be better in the combination arm when [the] planned regimen failed. Hematological toxicities were more common in the combination arm, although few patients discontinued due to toxicities in both arms," said presenter Tatsuro Fukuhara, MD, Miyagi Cancer Center.