Neoadjuvant Concurrent Chemo-immuno-radiation Therapy Followed by Surgery and Adjuvant Immunotherapy for Resectable Stage III N2 Non-Small Cell Lung Cancer: Primary Results from SQUAT trial (WJOG 12119L).
Akira Hamada: Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Department of Surgery II, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Junichi Soh: Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Department of Thoracic Surgery, Osaka Metropolitan University, Graduate School of Medicine, Osaka. Japan.
Akito Hata: Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan.
Kiyoshi Nakamatsu: Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Mototsugu Shimokawa: Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Yasushi Yatabe: Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
Jun Suzuki: Department of Surgery II, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Masahiro Tsuboi: Division of Thoracic Surgery, National Cancer Center Hospital East, Chiba, Japan.
Hidehito Horinouchi: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Yuichi Sakairi: Department of General Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Masayuki Tanahashi: Division of Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Japan.
Shinichi Toyooka: Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Morihito Okada: Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Natusmi Matsuura: Department of General Thoracic, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Hisayuki Shigematsu: Department of Thoracic Surgery, Shikoku Cancer Center, Matsuyama, Japan.
Yasumasa Nishimura: Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Nobuyuki Yamamoto: Department of Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
Kazuhiko Nakagawa: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Tetsuya Mitsudomi: Division of Thoracic Surgery, Department of Surgery, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Izumi City General Hospital, Izumi, Japan; Department of Innovative Medicine, Kindai University Faculty of Medicine, Osaka-Sayama, Japan. Electronic address: mitsudom@med.kindai.ac.jp.
INTRODUCTION: Neoadjuvant chemo-immunotherapy is one of the standard treatment options for resectable stage II-III non-small cell lung cancer (NSCLC). However, this treatment yielded insufficient local control in the CheckMate 816 trial. We hypothesized that adding radiotherapy could improve local control, thereby improving survival outcomes. METHODS: Eligible patients had clinical T1-3/T4 (tumor size) N2 stage IIIA-B NSCLC (AJCC ver. 8), pathologically confirmed as N2 without extranodal invasion. Patients received concurrent chemoradiotherapy (carboplatin [AUC 2] and paclitaxel [40 mg/ml] on days 1, 8, 15, 22, and 29, with 50 Gy radiation over 25 days) and durvalumab [1500 mg] on days 1 and 29, followed by surgical resection within 2-6 weeks. After surgery, durvalumab adjuvant therapy was administered for up to 1 year. The primary endpoint was major pathologic response (MPR: ≤10% viable tumor), with secondary endpoints being pathologic complete response (pCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: From January 2020 through February 2022, 31 patients were enrolled from 10 Japanese institutions. The MPR rate was 63% (90% CI: 47-78%), which met the primary endpoint, and the pCR rate was 23%. At a median follow-up of 28 months, the 2-year PFS and OS rates were 43% and 76%, respectively. Grade 3 or 4 adverse events occurred in 48% of cases, including one treatment-related death. CONCLUSIONS: Compared with recently published results of peri-operative chemo-immunotherapy trials, this treatment regimen had a higher MPR rate. However, this benefit did not necessarily translate into improved PFS or OS.
