Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101)
Naoya Nishioka, Hisao Imai, Masahiro Endo, Akifumi Notsu, Kosei Doshita, Satoshi Igawa, Hiroshi Yokouchi, Takashi Ninomiya, Takaaki Tokito, Sayo Soda, Takasato Fujiwara, Tetsuhiko Asao, Shinji Nakamichi, Takahisa Kawamura, Minehiko Inomata, Kazuhisa Nakashima, Kentaro Ito, Yasuhiro Gotô, Yukihiro Umeda, Soichi Hirai, Ryota Ushio, Keiki Yokoo, Takayuki Takeda, Tomoya Fukui, Masashi Ishihara, Takashi Osaki, Sousuke Kubo, Takumi Fujiwara, Chie Yamamoto, Takeshi Tsuda, Nobumasa Tamura, Shinobu Hosokawa, Yusuke Chihara, Satoshi Ikeda, Naoki Furuya, Yoshiro Nakahara, Satoru Miura, Hiroaki Okamoto
Abstract
BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.