Phase I Study Evaluating the Combination of Afatinib with Carboplatin and Pemetrexed After First-line EGFR-TKIs

Background/Aim: Promising reports have described the combination of first-generation epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) with carboplatin plus pemetrexed or bevacizumab. However, no analysis of afatinib with platinum-doublet chemotherapies has been performed. Patients and Methods: We evaluated the safety and antitumor efficacy of afatinib combined with carboplatin and pemetrexed in EGFR-mutated non-small-cell lung cancer (NSCLC) patients who progressed during first-generation EGFR-TKIs. Results: Ten patients received 20 or 30 mg/day afatinib with carboplatin (area under the curve, 5) and pemetrexed (500 mg/m(2)). Dose-limiting toxicities included delay of afatinib >= 14 days, grade 3 diarrhea, grade 3 hypokalemia, grade 3 serum amylase increase and grade 4 thrombocytopenia. The recommended dose of afatinib was 20 mg/day in this combination therapy. Overall response rate was 30% and median progression free survival was 13.7 months. Conclusion: This is the first study to investigate the combination of afatinib, carboplatin and pemetrexed. At the recommended dose, this combination was well tolerated and had a good clinical efficacy.