Hideo Saka1,2, Makoto Nishio3, Toyoaki Hida4, Kazuhiko Nakagawa5, Hiroshi Sakai6, Naoyuki Nogami7, Shinji Atagi8, Toshiaki Takahashi9, Hidehito Horinouchi10, Mitsuhiro Takenoyama11, Nobuyuki Katakami12, Hiroshi Tanaka13, Koji Takeda14, Miyako Satouchi15, Hiroshi Isobe16, Makoto Maemondo17,18, Koichi Goto19, Tomonori Hirashima20, Koichi Minato21, Nobumichi Yada22, Tomohide Tamura23. 1. Department of Medical Oncology, Nagoya Medical Center, Nagoya. 2. Department of Respiratory Medicine, Matsunami General Hospital, Gifu. 3. Department of Thoracic Medical Oncology, Cancer Institute Hospital, Tokyo. 4. Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya. 5. Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka. 6. Department of Thoracic Oncology, Saitama Cancer Center, Saitama. 7. Division of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Ehime. 8. Department of Thoracic Oncology, Kinki-Chuo Chest Medical Center, Sakai. 9. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka. 10. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo. 11. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka. 12. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe. 13. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 14. Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan. 15. Department of Thoracic Oncology, Hyogo Cancer Center, Hyogo, Japan. 16. Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan. 17. Division of Pulmonary Medicine, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan. 18. Department of Respiratory Medicine, Miyagi Cancer Center, Miyagi, Japan. 19. Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan. 20. Department of Thoracic Oncology, Osaka Habikino Medical Center, Osaka, Japan. 21. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Gunma, Japan. 22. Medical Affairs, Ono Pharmaceutical Co., Ltd, Osaka, Japan. 23. Thoracic Center, St. Luke's International Hospital, Tokyo, Japan.
Abstract
BACKGROUND: Two phase II studies in Japan examined the efficacy and safety of nivolumab, a programmed cell death 1 receptor inhibitor, in patients with advanced squamous and non-squamous non-small cell lung cancer (ONO-4538-05 and ONO-4538-06). We examined the long-term efficacy and safety of nivolumab in these patients treated for up to 5 years. METHODS: Patients with squamous (N = 35) or non-squamous (N = 76) non-small cell lung cancer received nivolumab (3 mg/kg every 2 weeks) until disease progression/death. Overall survival and progression-free survival were assessed at 5 years after starting treatment in separate and pooled analyses. Safety was evaluated in terms of treatment-related adverse events. RESULTS: A total of 17 patients were alive at the database lock (26 July 2019). The median overall survival (95% confidence interval) and 5-year survival rate were 16.3 (12.4-25.2) months and 14.3% in squamous patients, 17.1 (13.3-23.0) months and 19.4% in non-squamous patients and 17.1 (14.2-20.6) months and 17.8% in the pooled analysis, respectively. Programmed death ligand-1 expression tended to be greater among 5-year survivors than in non-survivors (P = 0.0703). Overall survival prolonged with increasing programmed death ligand-1 expression, with 5-year survival rates of 11.8, 21.8 and 41.7% in patients with programmed death ligand-1 expression of <1, ≥1-<50 and ≥50%, respectively. Treatment-related adverse events in ≥10% of patients (pooled analysis) included rash (15.3%), malaise (14.4%), decreased appetite (14.4%), pyrexia (14.4%) and nausea (10.8%). CONCLUSIONS: Long-term survival with nivolumab was observed in patients with squamous or non-squamous non-small cell lung cancer. No new safety signals were reported after ≥5 years of follow-up.
BACKGROUND: Two phase II studies in Japan examined the efficacy and safety of nivolumab, a programmed cell death 1 receptor inhibitor, in patients with advanced squamous and non-squamous non-small cell lung cancer (ONO-4538-05 and ONO-4538-06). We examined the long-term efficacy and safety of nivolumab in these patients treated for up to 5 years. METHODS:Patients with squamous (N = 35) or non-squamous (N = 76) non-small cell lung cancer received nivolumab (3 mg/kg every 2 weeks) until disease progression/death. Overall survival and progression-free survival were assessed at 5 years after starting treatment in separate and pooled analyses. Safety was evaluated in terms of treatment-related adverse events. RESULTS: A total of 17 patients were alive at the database lock (26 July 2019). The median overall survival (95% confidence interval) and 5-year survival rate were 16.3 (12.4-25.2) months and 14.3% in squamous patients, 17.1 (13.3-23.0) months and 19.4% in non-squamous patients and 17.1 (14.2-20.6) months and 17.8% in the pooled analysis, respectively. Programmed death ligand-1 expression tended to be greater among 5-year survivors than in non-survivors (P = 0.0703). Overall survival prolonged with increasing programmed death ligand-1 expression, with 5-year survival rates of 11.8, 21.8 and 41.7% in patients with programmed death ligand-1 expression of <1, ≥1-<50 and ≥50%, respectively. Treatment-related adverse events in ≥10% of patients (pooled analysis) included rash (15.3%), malaise (14.4%), decreased appetite (14.4%), pyrexia (14.4%) and nausea (10.8%). CONCLUSIONS: Long-term survival with nivolumab was observed in patients with squamous or non-squamous non-small cell lung cancer. No new safety signals were reported after ≥5 years of follow-up.
Authors: E E Vokes; N Ready; E Felip; L Horn; M A Burgio; S J Antonia; O Arén Frontera; S Gettinger; E Holgado; D Spigel; D Waterhouse; M Domine; M Garassino; L Q M Chow; G Blumenschein; F Barlesi; B Coudert; J Gainor; O Arrieta; J Brahmer; C Butts; M Steins; W J Geese; A Li; D Healey; L Crinò Journal: Ann Oncol Date: 2018-04-01 Impact factor: 32.976
Authors: Keith M Kerr; Ming-Sound Tsao; Andrew G Nicholson; Yasushi Yatabe; Ignacio I Wistuba; Fred R Hirsch Journal: J Thorac Oncol Date: 2015-07 Impact factor: 15.609
Authors: Julie Brahmer; Karen L Reckamp; Paul Baas; Lucio Crinò; Wilfried E E Eberhardt; Elena Poddubskaya; Scott Antonia; Adam Pluzanski; Everett E Vokes; Esther Holgado; David Waterhouse; Neal Ready; Justin Gainor; Osvaldo Arén Frontera; Libor Havel; Martin Steins; Marina C Garassino; Joachim G Aerts; Manuel Domine; Luis Paz-Ares; Martin Reck; Christine Baudelet; Christopher T Harbison; Brian Lestini; David R Spigel Journal: N Engl J Med Date: 2015-05-31 Impact factor: 91.245
Authors: Leora Horn; David R Spigel; Everett E Vokes; Esther Holgado; Neal Ready; Martin Steins; Elena Poddubskaya; Hossein Borghaei; Enriqueta Felip; Luis Paz-Ares; Adam Pluzanski; Karen L Reckamp; Marco A Burgio; Martin Kohlhäeufl; David Waterhouse; Fabrice Barlesi; Scott Antonia; Oscar Arrieta; Jérôme Fayette; Lucio Crinò; Naiyer Rizvi; Martin Reck; Matthew D Hellmann; William J Geese; Ang Li; Anne Blackwood-Chirchir; Diane Healey; Julie Brahmer; Wilfried E E Eberhardt Journal: J Clin Oncol Date: 2017-10-12 Impact factor: 44.544
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702