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

被引：99

作者：

Kobayashi, Tomoko ^{[1
]}

Iwama, Shintaro ^{[1
]}

Yasuda, Yoshinori ^{[1
]}

Okada, Norio ^{[1
]}

Okuji, Takayuki ^{[1
]}

Ito, Masaaki ^{[1
]}

Onoue, Takeshi ^{[1
]}

Goto, Motomitsu ^{[1
]}

Sugiyama, Mariko ^{[1
]}

Tsunekawa, Taku ^{[1
]}

Takagi, Hiroshi ^{[1
]}

Hagiwara, Daisuke ^{[1
]}

Ito, Yoshihiro ^{[1
,2
]}

Suga, Hidetaka ^{[1
]}

Banno, Ryoichi ^{[1
,3
]}

Yokota, Kenji ^{[4
]}

Hase, Tetsunari ^{[5
]}

Morise, Masahiro ^{[5
]}

Hashimoto, Naozumi ^{[5
]}

Ando, Masahiko ^{[6
]}

Fujimoto, Yasushi ^{[7
]}

Hibi, Hideharu ^{[8
]}

Sone, Michihiko ^{[7
]}

Ando, Yuichi ^{[9
]}

Akiyama, Masashi ^{[4
]}

Hasegawa, Yoshinori ^{[5
]}

Arima, Hiroshi ^{[1
]}

机构：

[1] Nagoya Univ, Dept Endocrinol & Diabet, Grad Sch Med, Nagoya, Aichi, Japan

[2] Nagoya Univ, Dept CKD Initiat Internal Med, Grad Sch Med, Nagoya, Aichi, Japan

[3] Nagoya Univ, Res Ctr Hlth Phys Fitness & Sports, Nagoya, Aichi, Japan

[4] Nagoya Univ, Dept Dermatol, Grad Sch Med, Nagoya, Aichi, Japan

[5] Nagoya Univ Grad Sch Med, Dept Resp Med, Nagoya, Aichi, Japan

[6] Nagoya Univ Hosp, Ctr Adv Med & Clin Res, Nagoya, Aichi, Japan

[7] Nagoya Univ, Dept Otorhinolaryngol, Grad Sch Med, Nagoya, Aichi, Japan

[8] Nagoya Univ, Dept Oral & Maxillofacial Surg, Grad Sch Med, Nagoya, Aichi, Japan

[9] Nagoya Univ Hosp, Dept Clin Oncol & Chemotherapy, Nagoya, Aichi, Japan

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2020年 / 8卷 / 02期

关键词：

immunotherapy; melanoma; lung neoplasms; ADVERSE EVENTS; NIVOLUMAB; HYPOPHYSITIS; IPILIMUMAB; IMMUNOTHERAPY; HYPONATREMIA; DIAGNOSIS;

D O I：

10.1136/jitc-2020-000779

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：8

共 33 条

[11] High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma [J].