S Sugawara1, J-S Lee2, J-H Kang3, H R Kim4, N Inui5, T Hida6, K H Lee7, T Yoshida8, H Tanaka9, C-T Yang10, M Nishio11, Y Ohe8, T Tamura12, N Yamamoto13, C-J Yu14, H Akamatsu13, Y Namba15, N Sumiyoshi16, K Nakagawa17. 1. Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan. 2. Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Korea. 3. Department of Medical Oncology, The Catholic University of Korea Seoul St. Mary's Hospital, Seoul, Korea. 4. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. 5. Department of Pulmonary Medicine, Hamamatsu University Hospital, Shizuoka, Japan. 6. Department of Thoracic Oncology, Aichi Cancer Center, Aichi, Japan. 7. Department of Internal Medicine, Chungbuk National University Hospital, Chungcheongbuk-do, Korea. 8. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 9. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 10. Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 11. Department of Thoracic Medical Oncology, Cancer Institute Hospital of JFCR, Tokyo, Japan. 12. Thoracic Center, St. Luke's International Hospital, Tokyo, Japan. 13. Internal Medicine III, Wakayama Medical University, Wakayama, Japan. 14. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 15. Clinical Science, Ono Pharmaceutical Co., Ltd., Osaka, Japan. 16. Oncology Clinical Development Planning 1, Ono Pharmaceutical Co., Ltd., Osaka, Japan. 17. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan. Electronic address: nakagawa@med.kindai.ac.jp.
Abstract
BACKGROUND: This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1 : 1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to six cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by an independent radiology review committee (IRRC). RESULTS: Overall, 550 patients from Japan, Korea, and Taiwan were randomized; of these patients, 273 and 275 received the nivolumab and placebo combinations, respectively. In the present preplanned interim analysis with a median follow up of 13.7 months, the IRRC-assessed median PFS was significantly longer in the nivolumab arm than in the placebo arm (12.1 versus 8.1 months; hazard ratio 0.56; 96.4% confidence interval 0.43-0.71; P < 0.0001). The PFS benefit was observed across all patients with any programmed death-ligand 1 (PD-L1) expression levels including PD-L1-negative patients. The IRRC-assessed objective response rates were 61.5% and 50.5% in the nivolumab and placebo arms, respectively. The incidence of treatment-related adverse events of grade 3 or 4 was comparable between the two arms; treatment-related adverse events leading to death were observed in five and four patients in the nivolumab and placebo arms, respectively. CONCLUSION: The TASUKI-52 regimen should be considered a viable new treatment strategy for treatment-naïve patients with advanced nonsquamous NSCLC.
BACKGROUND: This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1 : 1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to six cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by an independent radiology review committee (IRRC). RESULTS: Overall, 550 patients from Japan, Korea, and Taiwan were randomized; of these patients, 273 and 275 received the nivolumab and placebo combinations, respectively. In the present preplanned interim analysis with a median follow up of 13.7 months, the IRRC-assessed median PFS was significantly longer in the nivolumab arm than in the placebo arm (12.1 versus 8.1 months; hazard ratio 0.56; 96.4% confidence interval 0.43-0.71; P < 0.0001). The PFS benefit was observed across all patients with any programmed death-ligand 1 (PD-L1) expression levels including PD-L1-negative patients. The IRRC-assessed objective response rates were 61.5% and 50.5% in the nivolumab and placebo arms, respectively. The incidence of treatment-related adverse events of grade 3 or 4 was comparable between the two arms; treatment-related adverse events leading to death were observed in five and four patients in the nivolumab and placebo arms, respectively. CONCLUSION: The TASUKI-52 regimen should be considered a viable new treatment strategy for treatment-naïve patients with advanced nonsquamous NSCLC.
Authors: Yu Fujiwara; Nobuyuki Horita; Matthew Harrington; Ho Namkoong; Hirotaka Miyashita; Matthew D Galsky Journal: Cancer Immunol Immunother Date: 2022-04-26 Impact factor: 6.630