Five-year survival outcomes from the PIT-1 trial: Pemetrexed-cisplatin plus bevacizumab or concurrent thoracic radiation therapy followed by surgery in stage IIIA (N2) nonsquamous non-small cell lung cancer.

person Kazuya Takamochi Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan info_outline Kazuya Takamochi, Kenji Suzuki, Masahiro Tsuboi, Seiji Niho, Satoshi Ishikura, Shunsuke Oyamada, Takuhiro Yamaguchi, Hidemi Suzuki, Hiroyuki Ito, Norihito Okumura, Fumihiro Tanaka, Hisashi Saji, Terumoto Koike, Hirotoshi Horio, Makoto Endo, Toshiya Fujiwara, Norihiko Ikeda, Morihito Okada

Authors person Kazuya Takamochi Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan info_outline Kazuya Takamochi, Kenji Suzuki, Masahiro Tsuboi, Seiji Niho, Satoshi Ishikura, Shunsuke Oyamada, Takuhiro Yamaguchi, Hidemi Suzuki, Hiroyuki Ito, Norihito Okumura, Fumihiro Tanaka, Hisashi Saji, Terumoto Koike, Hirotoshi Horio, Makoto Endo, Toshiya Fujiwara, Norihiko Ikeda, Morihito Okada Organizations Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan, Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan, Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan, Division of Radiation Oncology, Tokyo Bay Makuhari Clinic for Advanced Imaging, Cancer Screening, and High-Precision Radiotherapy, Makuhari, Japan, Department of Biostatistics, Japanese Organisation for Research and Treatment of Cancer (JORTC) Data Center, Tokyo, Japan, Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan, Department of General Thoracic Surgery, Chiba University Graduate School of Medicin, Chiba, Japan, Division of Thoracic Surgery, Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan, Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan, University of Occupational and Environmental Health, Kitakyushu, Japan, Department of Thoracic Surgery, St. Marianna University School of Medicine, Kawasaki, Japan, Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, Department of Thoracic Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan, Department of Thoracic Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan, Department of Thoracic Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan, Department of Surgery, Tokyo Medical University, Tokyo, Japan, Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan Abstract Disclosures Research Funding No funding sources reported Background: Personized Induction Therapy-1 (PIT-1) is a multicenter, randomized phase II selection design trial of pemetrexed-cisplatin plus bevacizumab (BEV arm) or concurrent thoracic radiation therapy (TRT arm) followed by surgery in patients with stage IIIA (N2) nonsquamous non-small cell lung cancer (NSCLC). The TRT arm was chosen as the investigational induction treatment strategy for a future phase III study based on the results of a numerically higher 2-year progression-free survival (PFS, primary endpoint) in the TRT arm and fatal postoperative complications observed only in the BEV arm. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned. Methods: Patients with stage IIIA (N2) nonsquamous NSCLC were randomly assigned (1:1) induction therapy consisting of pemetrexed and cisplatin plus bevacizumab (n = 44) or concurrent TRT (n = 44) followed by surgery. Among them, 38 patients in the BEV arm and 37 patients in the TRT arm underwent surgery. Five-year overall survival (OS), 5-year PFS, and patterns of postoperative recurrence were compared between arms. Prognostic factors of OS were analyzed in surgically resected patients using Cox’s proportional hazard model. Results: The median follow-up was 66.4 months. In 82 treated patients, the 5-year OS and PFS rates were 63.5% (95% CI: 46.9-76.1) and 26.2% (95% CI: 14.1-40.0) in the BEV arm (n = 42), and 57.2% (95% CI: 40.5-70.8) and 27.5% (95% CI: 14.9-41.7) in the TRT arm (n = 40), respectively. There were no statistical differences in OS ( P = 0.572) and PFS ( P = 0.356). In 75 surgically resected patients, pathological nodal down stage was the only significant prognostic factor of OS ( P = 0.014). Age, sex, smoking status, clinical T stage, clinical N stage based on a computed tomography scan, preoperative serum CEA and CYFRA level, EGFR mutation status, pathological complete response, and major pathological response did not have a significant prognostic impact on OS. The patterns of postoperative recurrence were different between arms: locoregional only, in four (11%) and one (3%); distant metastasis only, in 16 (42%) and 21 (57%); and both, in five (13%) and four (11%) in the BEV and TRT arms, respectively. The recurrence rate of ipsilateral hilar or mediastinal lymph nodes (the irradiation field) was significantly lower in the TRT arm (3%) than in the BEV arm (21%, P = 0.01). Conclusions: Five-year survival outcomes were not different between the BEV and TRT arms. The TRT arm demonstrated sufficient local control, but insufficient control of distant metastasis so this is an important issue that requires improvement in the future. Clinical trial information: s031180402.

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