Association between diabetes mellitus and reduced efficacy of pembrolizumab in non–small cell lung cancer

Author:

Leshem Yasmin12ORCID,Dolev Yardenna1,Siegelmann‐Danieli Nava34,Sharman Moser Sarah3,Apter Lior35,Chodick Gabriel34,Nikolaevski‐Berlin Alla1,Shamai Sivan1,Merimsky Ofer1,Wolf Ido14

Affiliation:

1. Oncology Division Tel Aviv Sourasky Medical Center Tel Aviv Israel

2. Department of Immunology Weizmann Institute of Science Rehovot Israel

3. Maccabi Institute for Research and Innovation (Maccabitech) Maccabi Healthcare Services Tel Aviv Israel

4. Sackler School of Medicine Tel Aviv University Tel Aviv Israel

5. Department of Health Systems Management Ben‐Gurion University of the Negev Beer‐Sheva Israel

Abstract

AbstractBackgroundDiabetes mellitus (DM) is a highly prevalent chronic metabolic disorder. Although DM has been associated with immune dysfunction, the effect of DM on the efficacy of immunotherapy is unknown. This study aimed to evaluate the impact of DM on the efficacy of pembrolizumab in metastatic non–small cell lung cancer (NSCLC).MethodsThe authors reviewed the medical records of consecutive metastatic NSCLC patients treated with first‐line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center. For validation, a computerized data from Maccabi Healthcare Services, a 2.5–million‐member state health service was used.ResultsOf the 203 eligible patients, 51 (25%) had DM. Patients with DM had a significantly shorter median progression‐free survival (PFS) (5.9 vs. 7.1 months, p = .004) and overall survival (OS) (12 vs. 21 months, p = .006). The shorter OS in diabetic patients was more pronounced when pembrolizumab was given alone (12 vs. 27 months, p = .03) than when combined with chemotherapy (14.3 vs. 19.4 months, p = .06). Multivariate analysis confirmed DM as an independent risk factor for shorter PFS (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.11−2.50, p = .01) and OS (HR, 1.73; 95% CI, 1.09−2.76, p = .02). In a validation cohort of 452 metastatic NSCLC patients, the time on pembrolizumab treatment was shorter in diabetic patients (p = .025), with only 19.6% of patients remaining on treatment at 12 months compared to 31.7% of the nondiabetic patients.ConclusionsThis study suggests immunotherapy is less beneficial in diabetic NSCLC patients. More work is needed to verify our findings and explore similar effects in other cancer entities.

Publisher

Wiley

Subject

Cancer Research,Oncology

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