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ePoster Display

966P - Diabetes therapy burden as proxy of impairment of immune checkpoint inhibitors efficacy

Date

16 Sep 2021

Session

ePoster Display

Topics

Tumour Immunology;  Cancer Treatment in Patients with Comorbidities;  Clinical Research;  Immunotherapy;  Translational Research

Tumour Site

Presenters

Alessio Cortellini

Citation

Annals of Oncology (2021) 32 (suppl_5): S829-S866. 10.1016/annonc/annonc705

Authors

A. Cortellini1, D. Mallardo2, S. Cleary3, M. Bersanelli4, D. Santini5, M.G. Tucci6, A. Russo7, F. Rastelli8, M. Filetti9, A.J. Gelibter10, R. Marconcini11, R. Chiari12, F. Grossi13, M. De Tursi14, P. Queirolo15, F. Zoratto16, E.T. Tanda17, G. Porzio18, P.A. Ascierto19, D.J. Pinato20

Author affiliations

  • 1 Medical Oncology Dept., Ospedale Civile San Salvatore - ASL 1- Avezzano Sulmona L'Aquila, 67100 - L'Aquila/IT
  • 2 Melanoma, Cancer Immunotherapy And Development Therapeutics Department, Istituto Nazionale Tumori - IRCCS - Fondazione Pascale, 80131 - Napoli/IT
  • 3 Oncology Dept., Western Eye Hospital - Imperial College Healthcare Nhs Trust, NW1 5QH - London/GB
  • 4 Dipartimento Di Oncologia Medica, University Hospital of Parma, 43126 - Parma/IT
  • 5 Department Of Medical Oncology, Campus Bio-Medico University of Rome, 00128 - Italy/IT
  • 6 Medical Oncology Dept., Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, 70124 - Bari/IT
  • 7 Medical Oncology Dept., Centro Oncologico Ospedale Papardo, 98158 - Messina/IT
  • 8 Oncologia Day Hospital, Ospedale Ascoli Piceno "Mazzoni", 63100 - Ascoli PIceno/IT
  • 9 Medical Oncology, Sapienza, University of Rome, DPT Digestive and Liver Disease, Digestive Neuroendocrine Unit, 00189 - Rome/IT
  • 10 Department Of Radiology, Oncology And Pathology, Sapienza Università di Roma, 00161 - Rome/IT
  • 11 U.o. Oncologia Medica, Azienda Ospedaliera Universitaria S.Chiara, 56100 - Pisa/IT
  • 12 Medicine, Azienda Ospedaliera di Perugia S. Maria della Misericordia, 06132 - Perugia/IT
  • 13 Medical Oncology Division, University of Insubria, 21052 - Busto Arsizio/IT
  • 14 Medical Oncology Dept., Ospedale Clinicizzato SS. Annunziata - Chieti - Policlinico, 66100 - Chieti/IT
  • 15 Melanoma And Sarcoma Medical Treatment Unit, IEO - Istituto Europeo di Oncologia, 20141 - Milan/IT
  • 16 Medical Oncology Dept., Ospedale Santa Maria Goretti - ASL Latina, 04100 - Latina/IT
  • 17 Medical Oncology, IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT
  • 18 Department Of Medicine, St. Salvatore Hospital, 67100 - L'Aquila/IT
  • 19 Melanoma, Cancer Immunotherapy & Developmental Therapeutics, Istituto Nazionale Tumori - IRCCS - Fondazione Pascale, 80131 - Napoli/IT
  • 20 Surgery And Cancer, Imperial College London - Hammersmith Hospital, W12 0HS - London/GB

Resources

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Abstract 966P

Background

Chronic hyperglycemia is known to induce immune dysfunctions and multiple studies has identified resistance/adherence to insulin therapy as barriers to achieving an optimal glycaemic control in patients with diabetes mellitus (DM) after front line metformin failure. How DM affects the efficacy of immune checkpoint inhibitors (ICI) is yet to be defined.

Methods

We evaluated the impact of DM in a retrospective cohort of patients with advanced cancer treated with ICI at 22 Institutions. The diabetes medication burden (DMB) at ICI initiation was used as a proxy of long-term/poorly controlled DM. Patients with a high DMB were on high dose metformin (> 1000 mg) either alone or in combination with insulin therapy and/or other oral antidiabetics. Patients with low DMB were on oral antidiabetics/insulin with or without low dose metformin. In a subgroup of 133 patients the inter-relationships between the median baseline glycemia (MBG) (computed upon up to 3 fasting blood glucose tests within 3 months of ICI initiation) and the neutrophil-to-lymphocyte ratio (NLR) were assessed.

Results

From June 2014 to November 2020, 1395 patients treated with CTLA-4 (2.5%) and PD-1/PD-L1 (97.5%) inhibitors were included. Median age was 68 years; male/female ratio 888/507. Primary tumours were: NSCLC (54.7%), melanoma (24.7%), renal cell carcinoma (15.0%) and others (5.6%). 148 (10.6%) and 78 (5.6%) were on low and high DMB, respectively. The DMB was proportionally associated to both an increasing MBG (5.6, 7.5 and 9.5 mmol/L) and median NLR (3.8, 4.1 and 5.6). After adjusting for gender, age, BMI, primary tumour, treatment line, burden of disease, performance status and corticosteroids, patients on high DMB were confirmed to have shorter progression free survival (PFS) (HR 1.39[95%CI: 1.09-1.78] p=0.0075) and overall survival (OS) (HR 1.44 [95%CI:1.09-1.90] p = 0.0087) as compared to non-DM. MBG significantly predicted for the NLR [F(1,131) = 4.09, p = 0.04), R2 of .030], and was associated to a high NLR (≥ 4) even after adjusting for corticosteroids (OR = 1.68[95%CI: 1.23 – 2.29], p = 0.0011).

Conclusions

Long-term/poorly controlled diabetes may impair ICI efficacy. Strategies to improve glycaemic control should be pursued in patients about to start an immunotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University of L'Aquila.

Funding

Has not received any funding.

Disclosure

A. Cortellini: Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Expert Testimony: SunPharma; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. D.J. Pinato: Financial Interests, Personal, Speaker’s Bureau: ViiV Healthcare; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Board: EISAI; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.

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