Oncological Patients With Endocrine Complications After Immunotherapy With Checkpoint Inhibitors Present Longer Progression-Free and Overall Survival

Stavroula A Paschou; Michael Liontos; Evangelos Eleftherakis-Papaiakovou; Katerina Stefanaki; Christos Markellos; Konstantinos Koutsoukos; Flora Zagouri; Theodora Psaltopoulou; Meletios-Athanasios Dimopoulos

doi:10.3389/fonc.2022.847917

Oncological Patients With Endocrine Complications After Immunotherapy With Checkpoint Inhibitors Present Longer Progression-Free and Overall Survival

Front Oncol. 2022 Mar 24:12:847917. doi: 10.3389/fonc.2022.847917. eCollection 2022.

Authors

Stavroula A Paschou¹, Michael Liontos², Evangelos Eleftherakis-Papaiakovou², Katerina Stefanaki¹, Christos Markellos², Konstantinos Koutsoukos², Flora Zagouri², Theodora Psaltopoulou², Meletios-Athanasios Dimopoulos²

Affiliations

¹ Endocrine Unit and Diabetes Center, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
² Hematology and Oncology Unit, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

Aim: The aim of this study was to investigate the association of endocrine complications after ICI immunotherapy with progression-free survival (PFS) and overall survival (OS) in a large single-center oncological cohort.

Patients and methods: In total, 351 patients were included in the analysis, 248 men (70.7%) and 103 women (29.3%). The median age was 66 years. Patients had a variety of cancer types, namely, bladder cancer (131, 37.3%), renal cancer (89, 25.4%), lung cancer (74, 21.1%), ovarian cancer (22, 6.3%), and other types of cancer (35, 10%). The majority (314, 89.4%) were classified as stage IV, while 10.6% (37) were classified as stage III. Most of the patients received immunotherapy with anti-PD1 agents (262, 74.6%) and the rest with anti-PD-L1 agents (89, 25.4%). Kaplan-Meier estimates were used to describe and visualize the effect of categorical variables on OS and PFS. Survival analysis was performed by Kaplan-Meier curves, and survival differences between groups were estimated using the log-rank test. The estimation of the prognostic value of several variables with patients' survival was made by Cox regression models.

Results: In total, 68 (19.4%) of patients presented an endocrine complication after immunotherapy with ICIs. Specifically, 66 (18.8%) had thyroid dysfunction, 1 patient presented hypophysitis (0.3%), and 1 patient had a combination of thyroid dysfunction and hypophysitis (0.3%). Patients with an endocrine complication had mPFS of 15 months (95% CI 11.0-18.9 months), while in those without endocrine complication mPFS was 7 months (95% CI 6.1-7.9 months, p < 0.001). Similarly, median OS (mOS) was statistically significant lower in the patients' group without endocrine complication. In fact, mOS was 51 months (95% CI 39.3-62.7 months) for these patients. The presence of endocrine complications after immunotherapy with ICIs retained its significance in terms of longer PFS (HR 0.57, 95% CI 0.39-0.81) and OS (HR 0.53, 95% CI 0.32-0.90) after multivariate analysis.

Conclusions: ICI endocrinopathies may be a positive predictor of immunotherapy response.

Keywords: cancer; diabetes; endocrine; hypophysitis; immunotherapy; thyroiditis.