Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B) |
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Authors: | Tsubata Yukari Watanabe Kana Saito Ryota Nakamura Atsushi Yoshioka Hiroshige Morita Mami Honda Ryoichi Kanaji Nobuhiro Ohizumi Satoshi Jingu Daisuke Nakagawa Taku Nakazawa Kensuke Mouri Atsuto Takeuchi Susumu Furuya Naoki Akazawa Yuki Miura Kiyotaka Ichihara Eiki Maemondo Makoto Morita Satoshi Kobayashi Kunihiko Isobe Takeshi |
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Affiliation: | 1.Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan ;2.Department of Respiratory Medicine, Miyagi Cancer Center, 47-1, Nodayama, Medeshimashiote, Natori, Miyagi, 981-1293, Japan ;3.Department of Respiratory Medicine, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan ;4.Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15, Hirose-machi, Aoba-ku, Sendai, Miyagi, 980-0873, Japan ;5.Department of Thoracic Oncology, Kansai Medical University Hospital, 2-3-1, Shin-machi, Hirakata, Osaka, 573-1191, Japan ;6.Department of Respiratory Medicine, Asahi General Hospital, Asahi, Chiba, 1326289-2511, Japan ;7.Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kida-gun, Kagawa, 761-0793, Japan ;8.Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, 2-3-54, 4-jyo, Kikusui, Shiraisi-ku, Sapporo, Hokkaido, 003-0804, Japan ;9.Department of Respiratory Medicine, Saka General Hospital, 16-5, Nishiki-cho, Shiogama, Miyagi, 985-8506, Japan ;10.Department of Thoracic Surgery, Omagari Kosei Medical Center, 8-65, Toori-machi, Omagari, Daisen, Akita, 014-0027, Japan ;11.Division of Clinical Medicine, Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, 2-1-1, Amakubo, Tsukuba, Ibaraki, 305-8576, Japan ;12.Department of Respiratory Medicine, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama, 350-1298, Japan ;13.Division of General Thoracic and Thyroid Surgery, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku, Tokyo, 160-0023, Japan ;14.Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan ;15.Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1, Toneyama, Toyonaka, Osaka, 560-8552, Japan ;16.Department of Respiratory Medicine, Shimane Prefectural Central Hospital, 4-1-1, Himehara, Izumo, Shimane, 693-8555, Japan ;17.Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan ;18.Division of Pulmonary Medicine, Department of Internal Medicine, Iwate Medical University School of Medicine, 2-1-1, Idaidoori, Yahaba-cho, Shiwa-gun, Iwate, 028-3695, Japan ;19.Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54, Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan ; |
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Abstract: | Background Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. MethodsEnrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2–4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. ResultsThirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3–5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. ConclusionOsimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs. |
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