P3.02b-090 Pemetrexed versus Gefitinib in EGFR Mutation Positive Lung Cancer: Results of a Phase 3 Study from India

This study has been designed to confirm the efficacy of gefitinib Platinum and Pemetrexed combination chemotherapy as first-line treatment for advanced EGFR Mutation positive adenocarcinoma lung. This was an open label, randomized, parallel group study comparing Gefitinib ( 250 mg OD daily) with Platinum ( either Cisplatin 75 mg/m2 or Carboplatin AUC-5 ) and Pemetrexed ( 500 mg/m2 ) doublet intravenous chemotherapy regimen ( Induction of 4-6 cycles followed by maintenance) in patients with stage IIIB or stage IV adenocarcinoma lung who have confirmed to be EGFR activating mutation-positive in the first line setting. The primary endpoint for the study is progression free survival (PFS). Patients underwent axial imaging for response assessment on D42, D84, D126 and subsequently every 2 months till progression. Patients were followed up till death. For an estimated 50% improvement in progression free survival, with 80% power and 5% type one error, number of patients required will be 260. We expect a 5% dropout rate, which required 290 patients to be randomized. The median PFS in gefitinib arm was 8.433 months (95% CI 6.332-10.535) while it was 5.6 months (95% CI 4.207-6.993) in pemetrexed arm (p value-0.000, log rank test). The adjusted hazard ratio was 0.661 (95% CI 0.513- 0.852). The impact of gefitinib on PFS was seen across all subgroups Table 1. There was no statistically significant difference in overall survival between the 2 arms.Table 1Impact of gefitinib on progression free survival in different subgroupsVariableSubgroupHR95%CI HRP valueAgeBelow 65 years0.660.50-0.860.003Above 65 years0.350.18-0.680.002GenderMale0.660.47-0.920.014Female0.660.45-0.970.037SmokingSmoker0.600.34-1.040.071Non smoker0.600.45-0.790.000Oral tobacco useYes0.620.41-0.920.018No0.570.41-0.790.001ECOG PSPS0-10.620.48-0.820.001PS20.510.23-1.100.087Presence of liver metastasisYes0.550.33-0.910.020No0.630.48-0.850.002Presence of brain metastasisYes0.560.30-1.060.073No0.610.46-0.800.000 Open table in a new tab The study confirms superiority of gefitinib against the most active chemotherapy regimen of pemetrexed platinum in EGFR mutated NSCLC patients.