A Prospective Phase II Trial of First-line Osimertinib for Patients with EGFR Mutation-positive Non-small Cell Lung Cancer and Poor Performance Status (OPEN/TORG2040).
Tomoya Fukui, Nobuaki Mamesaya, Toshiaki Takahashi, Kazuma Kishi, Takahiro Yoshizawa, Takaaki Tokito, Koichi Azuma, Kei Morikawa, Satoshi Igawa, Yusuke Okuma, Yuta Yamanaka, Shinobu Hosokawa, Takashi Kasai, Ken Masubuchi, Shinji Nakamichi, Masaharu Aga, Jiichiro Sasaki, Akiko Kada, Akiko M Saito, Katsuhiko Naoki, Hiroaki Okamoto, Thoracic Oncology Research Group (TORG)
Author Information
Tomoya Fukui: Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan; Department of Respiratory Medicine, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa 247-8533, Japan. Electronic address: tofukui@med.kitasato-u.ac.jp.
Nobuaki Mamesaya: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
Toshiaki Takahashi: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
Kazuma Kishi: Department of Respiratory Medicine, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8541, Japan.
Takahiro Yoshizawa: Department of Respiratory Medicine, Toho University Omori Medical Center, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143-8541, Japan.
Takaaki Tokito: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
Koichi Azuma: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
Kei Morikawa: Department of Internal Medicine, Division of Respiratory Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
Satoshi Igawa: Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
Yusuke Okuma: Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Yuta Yamanaka: Department of Thoracic Oncology, Kansai Medical University Hospital, 2-3-1 Shinmachi, Hirakata, Osaka 573-1191, Japan.
Shinobu Hosokawa: Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, 2-1-1 Aoe, Kita-ku, Okayama, Okayama 700-8607, Japan.
Takashi Kasai: Division of Thoracic Oncology, Tochigi Cancer Center, 4-9-13 Yonan, Utsunomiya, Tochigi 320-0834, Japan.
Ken Masubuchi: Division of Respiratory Medicine, Gunma Prefectural Cancer Center, 617-1 Takahayashinishicho, Ota, Gunma 373-8550, Japan.
Shinji Nakamichi: Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Masaharu Aga: Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, 1-1 Mitsuzawa-Nishi-machi, Kanagawa-ku, Yokohama 221-0855, Japan.
Jiichiro Sasaki: Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
Akiko Kada: Clinical Research Center, NHO Nagoya Medical Center, 4-1-1 SannoMaru, Naka-ku, Nagoya, Aichi 460-0001, Japan.
Akiko M Saito: Clinical Research Center, NHO Nagoya Medical Center, 4-1-1 SannoMaru, Naka-ku, Nagoya, Aichi 460-0001, Japan.
Katsuhiko Naoki: Department of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
Hiroaki Okamoto: Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, 1-1 Mitsuzawa-Nishi-machi, Kanagawa-ku, Yokohama 221-0855, Japan.
INTRODUCTION: Osimertinib is the first-line treatment for patients with non-small cell lung cancer (NSCLC) who have EGFR mutations and favorable performance status (PS). Despite increasing clinical data on osimertinib, evidence in patients with an impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib for patients with EGFR mutation-positive NSCLC and poor PS. METHODS: Patients with previously untreated, advanced NSCLC harboring EGFR-sensitizing mutations and a PS of 2-4 were enrolled. Osimertinib, 80 mg once daily, was orally administered to eligible patients. The primary endpoint was the objective response rate. The secondary endpoints were the disease control rate, PS improvement rate, patient-reported outcomes, and safety. RESULTS: Between February 2021 and February 2022, 30 patients with poor PS (22 with PS of 2, 6 with PS of 3, and 2 with PS of 4) were enrolled. The median age was 75 years (range: 41-92), and 18 patients had brain metastases. The objective response rate was 63.3% (90% confidence interval, 46.7-77.9%; one-sided, p = 0.033). Disease control and PS improvement rates were 93.3% and 63.3%, respectively. Global health status/quality of life also improved. Median progression-free and overall survival were 8.0 and 25.4 months, respectively. Eight patients (26.7%) experienced serious adverse events leading to discontinuation, and six (20.0%) experienced interstitial lung disease (ILD). CONCLUSIONS: This prospective study confirmed the efficacy of first-line osimertinib in patients with EGFR mutation-positive NSCLC and poor PS, highlighting the need for ILD risk management.
