Diabetes Mellitus (DM) is Associated with Poor Outcome in Pembrolizumab-treated Non-small Cell Lung Cancer (NSCLC) Patients

Introduction:
Pembrolizumab and other Immune check-point inhibitors became the mainstay of treatment in ample malignancies, including NSCLC. Though DM causes immune dysfunction, the effect of DM on the efficacy of immunotherapy has not been addressed.

Methods:
Medical records of consecutive NSCLC patients treated with first-line pembrolizumab alone or combined with chemotherapy at Tel Aviv Medical Center from January 2017 to July 2021 were reviewed. We excluded patients who received a single cycle or were lost to follow-up.

Results:
Of 234 patients reviewed, 203 were included in the analysis. Their median age was 69 years, 128 were men (63%), 152 had adenocarcinoma (75%), and 51 patients had DM (25%). Diabetic patients were older (73 vs. 67, p <0.001) and had a higher mean body mass index (27 vs. 24, P<0.001). Median progression free survival (PFS) and overall survival (OS) were significantly shorter in diabetic compared to non-diabetic patients (5.9 vs. 7.1 months, respectively, P=0.004, and OS 12 vs. 21 months, respectively, p=0.006). The difference in OS was more pronounced for patients receiving pembrolizumab alone (12 vs. 27 months, p=0.03), than for those receiving pembrolizumab together with chemotherapy (14.3 vs. 19.4 months, p=0.06). Multivariate analysis indicated DM as an independent risk factor for inferior PFS (HR 1.7, 95% CI 1.11-2.5, p=0.014) and OS (HR 1.7, 95% CI 1.09-2.76, p=0.02).

Conclusions:
Here we show a potential deleterious effect of DM on the efficacy of pembrolizumab in metastatic NSCLC patients. If further validated, the administration of single agent pembrolizumab in this setting should be reconsidered.