ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P1027 | DOI: 10.1530/endoabs.63.P1027

Immune-related endocrine toxicities in non-small cell lung cancer: predictors of outcome to checkpoint inhibitors?

Roberta Poli1, Clement Dumont2, Lisa Pietrogiovanna3, Vincent Servois4, Sophie Beaucaire-Danel5, Catherine Daniel5, Nicolas Girard5, Emanuela Romano5,6,7 & Segolene Hescot6

1Department of Internal Medicine, Biella Hospital, Ponderano (BI), Italy; 2Department of Oncology, Saint-Louis Hospital, Paris, France; 3Department of Oncology, Biella Hospital, Ponderano (BI), Italy; 4Department of Radiology, Institut Curie, Paris & St. Cloud, France; 5Department of Oncology, Institut Curie, Paris & St. Cloud, France; 6Department of Drug Development and Innovation, Institut Curie, Paris & St. Cloud, France; 7Center of Cancer Immunotherapy, INSERM U932, PSL Research University, Institut Curie, Paris, France.

Background: Immune checkpoint inhibitors (ICIs) are approved for the treatment of non-small cell lung cancer (NSCLC) and are associated with specific immune-related adverse events (iRAEs) including endocrine toxicities. However, data concerning the type, occurrence, and dynamics of iRAEs and their predictive value on treatment outcome are lacking. In this study, we evaluated the relation of iRAEs to anti-PD/L1 (programmed cell death protein/ligand-1) ICIs focusing particularly on endocrine iRAEs.

Materials and methods: A total of 147 patients, with locally advanced/metastatic (stage IIIb and IV) NSCLC, treated with anti-PD1 (N 140; 95%) or anti-PDL1 agents (N 7; 5%) as ≥ 2 line treatment were included in two independent, prospective cohorts at the Institut Curie (ALCINA-NCT02866149) and at Biella Hospital (Italy). Progression free-survival (PFS) and overall survival (OS) were estimated with Kaplan-Meier curves.

Results: Among 147 patients, [median(range) age, 66 (35–85) years; 100 men (68%), 47 women (32%)], irAEs were observed in 72 patients (49%) including endocrine-irAEs, mostly thyroid dysfunctions, in 47 patients (32%). Pre-existing thyroid disease was present in 6 patients (4%), while type 2 diabetes mellitus (T2DM) was documented in 18 patients (12%). After treatment initiation, 64 patients had ≤ 2 coexisting irAEs (43%), and 8 had ≥ 2 toxicities (5%). Most iRAEs were G1 (N 71; 48%) and G2 (N 23; 16%). Median PFS was 5.7 and 3.1 months in irAEs vs no-irAEs group (P 0.11, NS), respectively. Median OS was significantly longer (23.4 months) in irAEs group compared with no-iRAEs group (13.5 months) [HR 0.59 (95% CI 0.35–1.0), P 0.049]. Moreover, median OS in the endocrine-iRAEs group was 29.83 vs 14.60 months in the no-iRAEs group, showing a trend toward significance in the association between endocrine-iRAEs and clinical outcome [HR 0.55 (95% CI 0.31–0.99), P 0.06, NS] possibly due to a lack of power.

Conclusions: Endocrine-irAEs are frequent in patients treated for NSCLC. In this study, we confirm that development of irAEs is a predictor of survival outcome in patients with advanced NSCLC treated with ICIs.