Kentaro Tanaka1, Hajime Asahina2, Junji Kishimoto3, Yoshihiro Miyata4, Takahiro Uchida5, Kana Watanabe6, Kosuke Hamai7, Taishi Harada8, Yukari Tsubata9, Shunichi Sugawara10, Kunihiko Kobayashi5, Kenji Sugio11, Satoshi Oizumi12, Isamu Okamoto13. 1. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. 3. Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan. 4. Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. 5. Division of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Japan. 6. Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Japan. 7. Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan. 8. Department of Respiratory Medicine, JCHO Kyushu Hospital, Kita-Kyushu, Japan. 9. Department of Internal Medicine, Division of Medical Oncology & Respiratory Medicine, Shimane University Faculty of Medicine, Izumo, Japan. 10. Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan. 11. Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan. 12. Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan. 13. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: okamotoi@kokyu.med.kyushu-u.ac.jp.
Abstract
BACKGROUND: Osimertinib is now a standard treatment for patients with previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC). We here investigated whether the combination of osimertinib with cytotoxic chemotherapy might hold additive efficacy, as well as tolerability. PATIENTS AND METHODS: We conducted an open-label randomised phase 2 study to evaluate osimertinib and carboplatin-pemetrexed combination in comparison with osimertinib monotherapy in EGFR mutation-positive NSCLC patients who experienced disease progression associated with the emergence of the T790M resistance mutation of EGFR during first-line EGFR-TKI therapy. The primary endpoint was PFS, with secondary endpoints, including OS, response, and safety. Given that osimertinib was approved as a first-line treatment during the study, patient accrual was discontinued, and a final analysis was performed for the 62 enrolled patients. RESULTS: Median PFS was 15.8 months for the osimertinib monotherapy group and 14.6 months for the combination therapy group (hazard ratio of 1.09, with a 95% confidence interval of 0.51-2.32; P = .83). Median OS was not reached in either group. The overall response rate was 71.4% in the osimertinib monotherapy group and 53.6% in the combination group. The frequency or severity of known adverse events in the combination group was comparable to those with carboplatin and pemetrexed previously reported, and novel adverse events were not observed in this study. CONCLUSION: This is the first randomised study to investigate the efficacy and safety of the combination of osimertinib and cytotoxic chemotherapy for EGFR-mutated NSCLC. The addition of chemotherapy to osimertinib as a second-line treatment did not prolong survival, while it was found to be generally tolerable. This combination strategy will be further validated in the first-line setting. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCTs071180062.
BACKGROUND: Osimertinib is now a standard treatment for patients with previously untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC). We here investigated whether the combination of osimertinib with cytotoxic chemotherapy might hold additive efficacy, as well as tolerability. PATIENTS AND METHODS: We conducted an open-label randomised phase 2 study to evaluate osimertinib and carboplatin-pemetrexed combination in comparison with osimertinib monotherapy in EGFR mutation-positive NSCLC patients who experienced disease progression associated with the emergence of the T790M resistance mutation of EGFR during first-line EGFR-TKI therapy. The primary endpoint was PFS, with secondary endpoints, including OS, response, and safety. Given that osimertinib was approved as a first-line treatment during the study, patient accrual was discontinued, and a final analysis was performed for the 62 enrolled patients. RESULTS: Median PFS was 15.8 months for the osimertinib monotherapy group and 14.6 months for the combination therapy group (hazard ratio of 1.09, with a 95% confidence interval of 0.51-2.32; P = .83). Median OS was not reached in either group. The overall response rate was 71.4% in the osimertinib monotherapy group and 53.6% in the combination group. The frequency or severity of known adverse events in the combination group was comparable to those with carboplatin and pemetrexed previously reported, and novel adverse events were not observed in this study. CONCLUSION: This is the first randomised study to investigate the efficacy and safety of the combination of osimertinib and cytotoxic chemotherapy for EGFR-mutated NSCLC. The addition of chemotherapy to osimertinib as a second-line treatment did not prolong survival, while it was found to be generally tolerable. This combination strategy will be further validated in the first-line setting. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCTs071180062.
Authors: Rolof G P Gijtenbeek; Vincent van der Noort; Joachim G J V Aerts; Jeske A Staal-van den Brekel; Egbert F Smit; Frans H Krouwels; Frank A Wilschut; T Jeroen N Hiltermann; Wim Timens; Ed Schuuring; Joost D J Janssen; Martijn Goosens; Paul M van den Berg; A Joop de Langen; Jos A Stigt; Ben E E M van den Borne; Harry J M Groen; Wouter H van Geffen; Anthonie J van der Wekken Journal: ERJ Open Res Date: 2022-10-17
Authors: Francesco Passiglia; Paolo Bironzo; Valentina Bertaglia; Angela Listì; Edoardo Garbo; Giorgio Vittorio Scagliotti Journal: Transl Lung Cancer Res Date: 2022-05