Daichi Fujimoto1, Hiroshige Yoshioka2, Yuki Kataoka3, Takeshi Morimoto4, 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 Medical Center for Adults, 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 has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials. METHODS: We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016. RESULTS: Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation - or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002). CONCLUSIONS: Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC.
INTRODUCTION:Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials. METHODS: We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016. RESULTS: Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation - or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade ≥3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade ≥3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002). CONCLUSIONS: Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC.
Authors: Jia Luo; Victoria L Martucci; Alexander Gusev; Melinda C Aldrich; Matthew D Hellmann; Elad Ziv; Zoe Quandt; Stefan Groha; Megan H Murray; Christine M Lovly; Hira Rizvi; Jacklynn V Egger; Andrew J Plodkowski; Mohsen Abu-Akeel; Isabell Schulze; Taha Merghoub; Eduardo Cardenas; Scott Huntsman; Min Li; Donglei Hu; Matthew A Gubens Journal: Clin Cancer Res Date: 2021-07-08 Impact factor: 12.531