A Retrospective Study for Prognostic Significance of Type II Diabetes Mellitus and Hemoglobin A1c Levels in Non-small Cell Lung Cancer Patients Treated with Pembrolizumab

Background: Diabetes mellitus (DM) is common and recognized as a risk factor for developing non-small cell lung cancer (NSCLC) while the prognostic evaluation is still controversial. As immunotherapy is widely used in clinical practice, its efficacy and survival should be investigated in patients with DM.

Methods: We retrospectively recruited 266 locally advanced and metastatic NSCLC patients who received pembrolizumab alone or in combination with chemotherapy. Patients' clinicopathological data, including age, history of DM, hemoglobin A1c (HbA1c), genetic tumor profiling, and survival data were collected. Associations between clinical characteristics and survival were evaluated by univariate and multivariate analyses.

Results: In this cohort, 15.04% (40/266) of the patients had a history of DM. Fifty-nine (22.2%) patients had a HbA1c level ≥6.5%. A total of 169 (63.5%) patients received 1st-line therapy, and 97 (36.5%) received 2nd- or subsequent-line therapy. Patients with high (≥6.5%) HbA1c and lower (<35 g/L) albumin levels at baseline had worse survivals, and epidermal growth factor receptor () mutants significantly associated with worse outcomes at normal HbA1c (<6.5%) levels (all P<0.05). Among the 1st-line therapy patients, a higher HbA1c level (≥6.5%) at baseline indicated a worse overall survival (OS) (2-year survival rate: 31.25% 27.03%, P=0.045), tumor protein p53 () alternations and high programmed death-ligand 1 (PD-L1) expression (≥50%) were significantly associated with better outcomes (P<0.05). For 2nd- or subsequent-line patients, mutants and non-squamous carcinomas (non-SCs) indicated worse survivals, and the normal peripheral blood markers of the carcinoembryonic antigen (CEA), C-reactive protein (CRP), albumin levels were favorable prognostic factors for survivals. In non-SCs, Kirsten rat sarcoma viral oncogene homolog () mutations, high PD-L1 expression, and normal alkaline phosphatase (ALP) levels favored better progression-free survival (PFS), while mutants indicated poor PFS (P<0.05).

Conclusions: Among patients treated with 1st-line immunotherapy, a higher HbA1c level (≥6.5%) indicated dismal OS, while history of DM, baseline blood glucose levels, and glucose changes during the treatment process were not significantly associated with any of the outcomes.