Go Saito1, Yuko Oya2, Yoshihiko Taniguchi3, Hayato Kawachi4, Fujimoto Daichi5, Hirotaka Matsumoto6, Shunichiro Iwasawa7, Hidekazu Suzuki8, Takayuki Niitsu9, Eisaku Miyauchi10, Takashi Yokoi11, Toshihide Yokoyama12, Takeshi Uenami13, Yoshihiko Sakata14, Daisuke Arai15, Asuka Okada16, Kenji Nagata17, Shunsuke Teraoka18, Masaki Kokubo19. 1. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan. 2. Department of Thoracic Oncology, Aichi Cancer Center, Aichi, Japan. Electronic address: yshima@aichi-cc.jp. 3. Department of Internal Medicine, Kinki-chuo Chest Medical Center, Osaka, Japan. 4. Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. 5. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan. 6. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan. 7. Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; Medical Sciences Department, Medical Affairs Division, Chugai Pharmaceutical Co., Ltd, Japan. 8. Department of Thoracic Oncology, Osaka Habikino Medical Center, Osaka, Japan. 9. Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan. 10. Department of Respiratory Medicine, Tohoku University Hospital, Miyagi, Japan. 11. Department of Thoracic Oncology, Hyogo College of Medicine, Hyogo, Japan. 12. Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama, Japan. 13. Department of Thoracic Oncology, National Hospital Organization, Toneyama National Hospital, Osaka, Japan. 14. Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan. 15. Pulmonary Division, Department Internal Medicine, Saiseikai Utsunomiya Hospital, Tochigi, Japan. 16. Department of Respiratory Medicine, Saiseikai Suita Hospital, Osaka, Japan. 17. Department of Respiratory Medicine, Itami City Hospital, Hyogo, Japan. 18. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. 19. Department of Radiation Oncology, Kobe City Medical Center General Hospital, Hyogo, Japan.
Abstract
OBJECTIVES: The incidence of real-world pneumonitis and durvalumab rechallenge during chemoradiotherapy and durvalumab consolidation for non-small cell lung cancer is unknown. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 302 consecutive patients diagnosed with non-small cell lung cancer who started chemoradiotherapy between May 2018 and May 2019. RESULTS: Median age was 70 (range: 40-87) years. Volume of lung parenchyma that received 20 Gy (V20) exceeded 35% in 2% and mean lung dose exceeded 20 Gy in 1% of patients. Durvalumab consolidation was delivered to 225 patients (75%). Overall, 83% (n = 251), 34% (n = 103), 7% (n = 21), and 1% (n = 4) of the patients developed any grade of pneumonitis, symptomatic pneumonitis, ≥grade 3 pneumonitis, and fatal (grade 5) pneumonitis, respectively. Corticosteroids were administered to 25% of the patients to treat pneumonitis. Multivariate analysis identified the predictive factors for the development of symptomatic pneumonitis: V20 Gy or more ≥ 25% (odds ratio [OR]: 2.37, P = 0.008) and mean lung dose (MLD) ≥ 10 Gy (OR: 1.93, P < 0.0047). Of the 52 patients who received corticosteroids for pneumonitis after durvalumab initiation, 21 were rechallenged with durvalumab. Overall, 81% of patients met the PACIFIC study's rechallenge criteria and did not experience a severe pneumonitis relapse. CONCLUSION: High V20 and MLD were independent risk factors of symptomatic pneumonitis. More than 80% of the patients who were rechallenged with durvalumab after pneumonitis met the PACIFIC study's rechallenge criteria. Consequently, severe relapse did not occur. Cooperation between radiation and medical oncologists is important for safe chemoradiotherapy and the safe completion of durvalumab consolidation therapy.
OBJECTIVES: The incidence of real-world pneumonitis and durvalumab rechallenge during chemoradiotherapy and durvalumab consolidation for non-small cell lung cancer is unknown. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 302 consecutive patients diagnosed with non-small cell lung cancer who started chemoradiotherapy between May 2018 and May 2019. RESULTS: Median age was 70 (range: 40-87) years. Volume of lung parenchyma that received 20 Gy (V20) exceeded 35% in 2% and mean lung dose exceeded 20 Gy in 1% of patients. Durvalumab consolidation was delivered to 225 patients (75%). Overall, 83% (n = 251), 34% (n = 103), 7% (n = 21), and 1% (n = 4) of the patients developed any grade of pneumonitis, symptomatic pneumonitis, ≥grade 3 pneumonitis, and fatal (grade 5) pneumonitis, respectively. Corticosteroids were administered to 25% of the patients to treat pneumonitis. Multivariate analysis identified the predictive factors for the development of symptomatic pneumonitis: V20 Gy or more ≥ 25% (odds ratio [OR]: 2.37, P = 0.008) and mean lung dose (MLD) ≥ 10 Gy (OR: 1.93, P < 0.0047). Of the 52 patients who received corticosteroids for pneumonitis after durvalumab initiation, 21 were rechallenged with durvalumab. Overall, 81% of patients met the PACIFIC study's rechallenge criteria and did not experience a severe pneumonitis relapse. CONCLUSION: High V20 and MLD were independent risk factors of symptomatic pneumonitis. More than 80% of the patients who were rechallenged with durvalumab after pneumonitis met the PACIFIC study's rechallenge criteria. Consequently, severe relapse did not occur. Cooperation between radiation and medical oncologists is important for safe chemoradiotherapy and the safe completion of durvalumab consolidation therapy.