Hajime Asahina1, Kentaro Tanaka2, Satoshi Morita3, Makoto Maemondo4, Masahiro Seike5, Isamu Okamoto2, Satoshi Oizumi6, Hiroshi Kagamu7, Kazuhisa Takahashi8, Toshiaki Kikuchi9, Takeshi Isobe10, Kenji Sugio11, Kunihiko Kobayashi12. 1. Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 2. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 4. Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan. 5. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. 6. Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan. 7. Division of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan. 8. Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 9. Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 10. Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan. 11. Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan. 12. Division of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan. Electronic address: kobakuni@saitamamed.ac.jp.
Abstract
BACKGROUND: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is now a standard treatment of previously untreated EGFR-mutated advanced non-small-cell lung cancer (NSCLC). However, disease progression occurs within 19 months of treatment. In the NEJ009 study, gefitinib plus carboplatin plus pemetrexed demonstrated significantly better progression-free and overall survival compared with gefitinib monotherapy. Furthermore, the Lung Oncology Group in Kyushu and North East Japan Study Group, major clinical trial groups in Japan, conducted a randomized phase II study to evaluate the efficacy and safety of second-line osimertinib plus carboplatin plus pemetrexed versus osimertinib monotherapy for patients with disease progression during first-line EGFR tyrosine kinase inhibitor therapy and the EGFR T790M resistance mutation (TAKUMI trial; trial registration no., jRCTs071180062). In the first treatment course for the initial 24 patients, no safety issues were reported in the combination arm. Thus, we have planned this phase II study to evaluate the safety and preliminary efficacy of osimertinib plus cisplatin/carboplatin plus pemetrexed therapy for patients with previously untreated EGFR-mutated NSCLC. PATIENTS AND METHODS: A total of 66 patients will be enrolled, because this sample size will be adequate for assessing treatment safety and efficacy. The co-primary endpoints include safety and the objective response rate, and the secondary endpoints include the complete response rate, disease control rate, and progression-free survival. CONCLUSIONS: This is the first study to explore the efficacy and safety of osimertinib combined with platinum-based chemotherapy in previously untreated NSCLC patients with EGFR-sensitizing mutations. Our findings could provide valuable information for phase III studies such as FLAURA2 and for developing treatment strategies for EGFR-mutated NSCLC.
BACKGROUND: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is now a standard treatment of previously untreated EGFR-mutated advanced non-small-cell lung cancer (NSCLC). However, disease progression occurs within 19 months of treatment. In the NEJ009 study, gefitinib plus carboplatin plus pemetrexed demonstrated significantly better progression-free and overall survival compared with gefitinib monotherapy. Furthermore, the Lung Oncology Group in Kyushu and North East Japan Study Group, major clinical trial groups in Japan, conducted a randomized phase II study to evaluate the efficacy and safety of second-line osimertinib plus carboplatin plus pemetrexed versus osimertinib monotherapy for patients with disease progression during first-line EGFR tyrosine kinase inhibitor therapy and the EGFR T790M resistance mutation (TAKUMI trial; trial registration no., jRCTs071180062). In the first treatment course for the initial 24 patients, no safety issues were reported in the combination arm. Thus, we have planned this phase II study to evaluate the safety and preliminary efficacy of osimertinib plus cisplatin/carboplatin plus pemetrexed therapy for patients with previously untreated EGFR-mutated NSCLC. PATIENTS AND METHODS: A total of 66 patients will be enrolled, because this sample size will be adequate for assessing treatment safety and efficacy. The co-primary endpoints include safety and the objective response rate, and the secondary endpoints include the complete response rate, disease control rate, and progression-free survival. CONCLUSIONS: This is the first study to explore the efficacy and safety of osimertinib combined with platinum-based chemotherapy in previously untreated NSCLC patients with EGFR-sensitizing mutations. Our findings could provide valuable information for phase III studies such as FLAURA2 and for developing treatment strategies for EGFR-mutated NSCLC.