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Can Diabetes Affect the Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Cancer?


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Investigators from 22 institutions aimed to evaluate the impact of diabetes mellitus in a retrospective cohort of patients with advanced cancer treated with a single-agent immune checkpoint inhibitor. In a report presented by Cortellini et al at the European Society for Medical Oncology (ESMO) Congress 2021, the researchers said that long-term or poorly controlled diabetes may impair the efficacy of such therapies (Abstract 966P).

In the study background, the authors explained that chronic hyperglycemia induces immune dysfunction. Furthermore, multiple studies have identified resistance or adherence to insulin therapy as barriers to achieving optimal glycemic control in patients with diabetes mellitus after front-line metformin failure.

Study Methods

In this study, researchers evaluated the impact of diabetes mellitus in patients with advanced cancer treated with immune checkpoint inhibitors. They used diabetes medication burden at initiation of treatment with immunotherapy as a proxy of long-term or poorly controlled diabetes mellitus. Patients with a high diabetes medication burden were on high-dose metformin (more than 1,000 mg) either alone or in combination with insulin therapy and/or other oral antidiabetic agents. Patients with a low diabetes medication burden were on oral antidiabetic agents or insulin with or without low-dose metformin.

Long-term/poorly controlled diabetes may impair immune checkpoint inhibitor efficacy. Strategies to improve glycemic control should be pursued in patients about to start an immunotherapy.
— Cortellini et al

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In a subgroup of 133 patients, the interrelationships between median baseline glycemia and the neutrophil-to-lymphocyte ratio were assessed.

Nearly 1,400 patients who were treated with CTLA-4 (2.5%) and PD-1/PD-L1 (97.5%) inhibitors from June 2014 to November 2020 were included in the analysis. The median age was 68 years; 888 male patients and 507 female patients were included in the cohort. The primary tumor types were non–small cell lung cancer (54.7% of patients), melanoma (24.7%), renal cell carcinoma (15.0%), and other cancer type (5.6%).

Results

In total, 148 patients (10.6%) were classified as having a low diabetes medication burden and 78 patients (5.6%), a high diabetes medication burden. Diabetes medication burden was proportionally associated with both increasing median baseline glycemia (5.6, 7.5, and 9.5 mmol/L) and median neutrophil-to-lymphocyte ratio (3.8, 4.1, and 5.6).

After adjusting for sex, age, body mass index, primary tumor, treatment line, burden of disease, performance status, and corticosteroid use, patients with a high diabetes medication burden had shorter progression-free survival (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.09–1.78, P = .0075) and overall survival (HR = 1.44, 95% CI = 1.09–1.90, P = .0087) as compared with those without diabetes.

Median baseline glycemia significantly predicted the neutrophil-to-lymphocyte ratio and was associated with a high neutrophil-to-lymphocyte, even after adjusting for corticosteroids.

The study authors concluded: “Long-term/poorly controlled diabetes may impair immune checkpoint inhibitor efficacy. Strategies to improve glycemic control should be pursued in patients about to start an immunotherapy.”

Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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