PT  - JOURNAL ARTICLE
AU  - Kobayashi, Tomoko
AU  - Iwama, Shintaro
AU  - Yasuda, Yoshinori
AU  - Okada, Norio
AU  - Okuji, Takayuki
AU  - Ito, Masaaki
AU  - Onoue, Takeshi
AU  - Goto, Motomitsu
AU  - Sugiyama, Mariko
AU  - Tsunekawa, Taku
AU  - Takagi, Hiroshi
AU  - Hagiwara, Daisuke
AU  - Ito, Yoshihiro
AU  - Suga, Hidetaka
AU  - Banno, Ryoichi
AU  - Yokota, Kenji
AU  - Hase, Tetsunari
AU  - Morise, Masahiro
AU  - Hashimoto, Naozumi
AU  - Ando, Masahiko
AU  - Fujimoto, Yasushi
AU  - Hibi, Hideharu
AU  - Sone, Michihiko
AU  - Ando, Yuichi
AU  - Akiyama, Masashi
AU  - Hasegawa, Yoshinori
AU  - Arima, Hiroshi
TI  - 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
AID  - 10.1136/jitc-2020-000779
DP  - 2020 Jul 01
TA  - Journal for ImmunoTherapy of Cancer
PG  - e000779
VI  - 8
IP  - 2
4099  - http://jitc.bmj.com/content/8/2/e000779.short
4100  - http://jitc.bmj.com/content/8/2/e000779.full
SO  - J Immunother Cancer2020 Jul 01; 8
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.