Chemotherapy Effectiveness After First-Line Gefitinib Treatment for Advanced Lepidic Predominant Adenocarcinoma (Formerly Advanced Bronchioloalveolar Carcinoma): Exploratory Analysis of the IFCT-0401 Trial

Abstract

This study explored whether chemotherapy after first-line gefitinib was effective in patients with advanced lepidic predominant adenocarcinoma (LPA), formerly advanced bronchioloalveolar carcinoma, who were enrolled in the Intergroupe Francophone de Cancérologie Thoracique (IFCT)-0401 trial. Overall, 88 patients presenting advanced LPA were enrolled in the IFCT-0401 trial, receiving gefitinib as first-line therapy. No predefined second-line treatment was mandatory in the case of progression or limiting toxicity under gefitinib. However, the carboplatin plus paclitaxel regimen was recommended for patients with a performance status (PS) 0 or 1 and gemcitabine monotherapy for those with a PS 2. For these patients, data concerning treatment efficacy was collected from the IFCT-0401 trial database. In total, 47 patients (53%) received second-line treatment after the failure of gefitinib, with 43 having PS 0 or 1. Regarding treatment, 43 were treated with chemotherapy, with 38 receiving a platinum-doublet regimen (taxane-based, n = 29; gemcitabine-based, n = 9) and five receiving monotherapy (gemcitabine, n = 3; pemetrexed, n = 2). The overall response rate (ORR) to chemotherapy was 21% (95% confidence interval [CI]: 10-36), disease control rate 56% (95% CI: 40-71), and median progression-free survival (PFS) 3.0 months (95% CI: 2.4-4.9). For patients receiving a platinum doublet (n = 38), ORR was 21% (95% CI: 10-37), with disease control rate being 55% (95% CI: 38-71), and median PFS 2.9 months (95% CI: 2.4-4.4). For patients receiving taxane-based regimen (n = 29) and gemcitabine-based regimen (n = 12), ORR was 28% and 0%, respectively, with a median PFS of 3.3 and 2.0 months, respectively, (p = 0.0243). The two patients receiving pemetrexed experienced a prolonged response. Multivariate Cox model analysis revealed that only the use of taxane-based chemotherapy or pemetrexed was related to PFS. Platinum-doublet chemotherapy showed some effectiveness in treating advanced LPA patients after first-line gefitinib. Our findings also suggest that taxane-based chemotherapy and pemetrexed should be investigated further in future clinical trials.