ECE2023 Poster Presentations Endocrine-related Cancer (62 abstracts)
Association between diabetes mellitus and reduced efficacy of pembrolizumab in non-small cell lung cancer
Yasmin Leshem 1 , Yardena Dolev 1 , Nava Siegelmann-Danieli 2 , Sarah Sharman Moser 2 , Lior Apter 2 , Gabriel Chodick 2 , Alla Nikolaevski-Berlin 1 , Sivan Shamai 1 , Ofer Merimsky 1 & Ido Wolf 1
1Tel Aviv Medical Center, Oncology, Tel Aviv, Israel; 2Maccabi Healthcare Services, Maccabitech, Tel Aviv, Israel
Introduction: Type 2 diabetes mellitus (T2DM) and cancer commonly occur together, either because of direct association or merely as both diseases are common among the elderly. The presence of either T2DM itself, or its treatment may affect cancer progression outcomes and response to cancer therapy. Immune-checkpoint inhibitors (ICIs) have become the cornerstone of treatment of several malignancies, including non-small cell lung cancer (NSCLC). As T2DM has been shown to suppress activity of the immune system, we hypothesized that it will impair the activity of ICIs.
Methods: Medical records of all consecutive patients with advanced NSCLC, treated with first-line pembrolizumab either alone or in combination with chemotherapy at Tel Aviv Medical Center (TLVMC) were reviewed. Data on a similar group of patients was extracted from the computerized data of a large Israeli HMO, from Maccabi Healthcare Services (MHS), with over 2.5- million-member.
Results: Two hundred and three eligible NSCLC patients were identified, 51 of them (25%) had T2DM. Compared to patients without DM, patients with DM had a significantly shorter median progression-free survival (PFS; 5.9 vs. 7.1 months, P=0.004) and overall survival (OS; 12 vs. 21 months, P=0.006). The differences in OS were significantly more pronounced for patients being treated with pembrolizumab as single agent (12 vs. 27 months, for DM vs. Non-DM, P=0.03) but was of borderline significance for those receiving immunotherapy and chemotherapy (14.3 vs. 19.4 months, for DM vs. Non-DM, P=0.06). Multivariate analysis indicated DM as an independent risk factor for lower PFS (HR 1.67, 95% CI 1.11−2.50, P=0.01) and lower OS (HR 1.73, 95% CI 1.09−2.76, P=0.02). A cohort of 452 metastatic NSCLC patients was identified at MHS database. Similarly to the TLVMC cohort, shorter time on treatment was noted for DM compared to non-DM patients, with only 19.6% of patients remaining on treatment at 12 months compared to 31.7% of the non-diabetic patients (P=0.025).
Conclusions: These data indicate an adverse effect of T2DM on the efficacy of pembrolizumab in patients with advanced NSCLC. While additional studies are required to better define this association, it is possible that our observation is relevant to other malignancies, as well as other types of ICIs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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