RT Journal Article
SR Electronic
T1 Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000779
DO 10.1136/jitc-2020-000779
VO 8
IS 2
A1 Kobayashi, Tomoko
A1 Iwama, Shintaro
A1 Yasuda, Yoshinori
A1 Okada, Norio
A1 Okuji, Takayuki
A1 Ito, Masaaki
A1 Onoue, Takeshi
A1 Goto, Motomitsu
A1 Sugiyama, Mariko
A1 Tsunekawa, Taku
A1 Takagi, Hiroshi
A1 Hagiwara, Daisuke
A1 Ito, Yoshihiro
A1 Suga, Hidetaka
A1 Banno, Ryoichi
A1 Yokota, Kenji
A1 Hase, Tetsunari
A1 Morise, Masahiro
A1 Hashimoto, Naozumi
A1 Ando, Masahiko
A1 Fujimoto, Yasushi
A1 Hibi, Hideharu
A1 Sone, Michihiko
A1 Ando, Yuichi
A1 Akiyama, Masashi
A1 Hasegawa, Yoshinori
A1 Arima, Hiroshi
YR 2020
UL http://jitc.bmj.com/content/8/2/e000779.abstract
AB Background Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM).Methods A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint.Results Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05).Conclusions In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone.Clinical trials registration UMIN000019024.