Daichi Fujimoto1, Hiroshige Yoshioka2, Yuki Kataoka3, Takeshi Morimoto4, Tae Hata2, Young Hak Kim5, Keisuke Tomii6, Tadashi Ishida2, Masataka Hirabayashi3, Satoshi Hara7, Manabu Ishitoko8, Yasushi Fukuda9, Moon Hee Hwang10, Naoki Sakai11, Motonari Fukui12, Hitoshi Nakaji13, Mitsunori Morita14, Tadashi Mio15, Takehiro Yasuda16, Takakazu Sugita17, Toyohiro Hirai5. 1. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. Electronic address: daichi@kcho.jp. 2. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan. 3. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan. 4. Clinical Research Center, Kobe City Medical Center General Hospital, Kobe, Japan; Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan. 5. Department of Respiratory Medicine, Kyoto University Hospital, Kyoto, Japan. 6. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 7. Department of Respiratory Medicine, Itami City Hospital, Itami, Japan. 8. Department of Respiratory Medicine, Shiga General Hospital, Moriyama, Japan. 9. Department of Respiratory Medicine, Himeji Medical Center, Himeji, Japan. 10. Department of Respiratory Medicine, Osaka Red Cross Hospital, Osaka, Japan. 11. Department of Respiratory Medicine, Otsu Red Cross Hospital, Otsu, Japan. 12. Respiratory Disease Center, Kitano Hospital, The Tazuke-Kofukai Medical Research Institute, Osaka, Japan. 13. Department of Respiratory Medicine, Toyooka Public Hospital, Toyooka, Japan. 14. Department of Respiratory Medicine, Kobe City Medical Center West Hospital, Kobe, Japan. 15. Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan. 16. Department of Respiratory Medicine, Tenri Hospital, Nara, Japan. 17. Department of Respiratory Medicine, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan.
Abstract
INTRODUCTION: Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression. METHODS: We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death. RESULTS: Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001). CONCLUSIONS: Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression.
INTRODUCTION:Nivolumab is effective in the treatment of previously treated patients with advanced NSCLC. However, its radiological evaluation is challenging because of atypical patterns of response such as pseudoprogression. We examined the characteristics and outcomes of previously treated patients with NSCLC who were treated with nivolumab and experienced development of pseudoprogression. METHODS: We conducted a 15-center retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab monotherapy. For the patients who showed pseudoprogression, we defined progression-free survival 1 (PFS1) as the time to Response Evaluation Criteria in Solid Tumors-defined first progressive disease and progression-free survival 2 (PFS2) as the time to Response Evaluation Criteria in Solid Tumors-defined second progressive disease or death. RESULTS: Among the 542 patients included, 20% and 53% showed a typical response and progression, respectively. Of the 14 (3%) patients who showed pseudoprogression, most (n = 10) showed a response within 3 months of nivolumab treatment. The median PFS1 and PFS2 were 1.0 and 7.3 months, respectively. The median PFS2 was significantly shorter in the patients who showed pseudoprogression than the PFS of the patients with a typical response (p < 0.001). In contrast, patients showing pseudoprogression had significantly longer overall survival than did patients showing typical progression (p = 0.001). CONCLUSIONS: Pseudoprogression was uncommon, and the duration of response in patients who showed pseudoprogression was shorter than that in patients who showed a typical response. However, the survival benefit of pseudoprogression was markedly better than that of typical progression. Further research is required to elucidate the characteristics of and mechanisms underlying pseudoprogression.
Authors: Kathryn C Arbour; Anh Tuan Luu; Jia Luo; Justin F Gainor; Regina Barzilay; Matthew D Hellmann; Hira Rizvi; Andrew J Plodkowski; Mustafa Sakhi; Kevin B Huang; Subba R Digumarthy; Michelle S Ginsberg; Jeffrey Girshman; Mark G Kris; Gregory J Riely; Adam Yala Journal: Cancer Discov Date: 2020-09-21 Impact factor: 39.397