Concurrent Nivolumab and Metformin in Diabetic Cancer Patients: Is It Safe and More Active?


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Mar 2022
Historique:
received: 29 11 2021
revised: 10 01 2022
accepted: 12 01 2022
entrez: 27 2 2022
pubmed: 28 2 2022
medline: 8 3 2022
Statut: ppublish

Résumé

Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin. The aim of this study was to investigate the safety and activity of metformin combined with nivolumab in diabetic cancer patients. Patients with advanced melanoma, renal cell carcinoma or lung cancer receiving nivolumab with concurrent diabetes treated with metformin were retrospectively collected. The primary endpoint was the safety of nivolumab plus metformin combination. We collected 40 patients with solid tumors who received metformin for concomitant diabetes and nivolumab as anticancer therapy in four Italian Hospitals. The concomitant use of nivolumab and metformin was well tolerated; adverse events (AEs) of any grade occurred in 75% of patients (mainly fatigue, pruritus, rash, and asthenia). Grade 3 AEs occurred only in 20% of cases; no grade 4 AEs were observed. A statistically significant correlation was found between higher doses of metformin (>1,000 mg daily) and longer progression-free survival (p=0.021), overall survival (p=0.037) and higher overall response rate. The combination of nivolumab and metformin was safe and might have an antitumor activity, supporting further investigations on the synergistic antitumor effect of this combination.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin. The aim of this study was to investigate the safety and activity of metformin combined with nivolumab in diabetic cancer patients.
PATIENTS AND METHODS METHODS
Patients with advanced melanoma, renal cell carcinoma or lung cancer receiving nivolumab with concurrent diabetes treated with metformin were retrospectively collected. The primary endpoint was the safety of nivolumab plus metformin combination.
RESULTS RESULTS
We collected 40 patients with solid tumors who received metformin for concomitant diabetes and nivolumab as anticancer therapy in four Italian Hospitals. The concomitant use of nivolumab and metformin was well tolerated; adverse events (AEs) of any grade occurred in 75% of patients (mainly fatigue, pruritus, rash, and asthenia). Grade 3 AEs occurred only in 20% of cases; no grade 4 AEs were observed. A statistically significant correlation was found between higher doses of metformin (>1,000 mg daily) and longer progression-free survival (p=0.021), overall survival (p=0.037) and higher overall response rate.
CONCLUSION CONCLUSIONS
The combination of nivolumab and metformin was safe and might have an antitumor activity, supporting further investigations on the synergistic antitumor effect of this combination.

Identifiants

pubmed: 35220243
pii: 42/3/1487
doi: 10.21873/anticanres.15620
doi:

Substances chimiques

B7-H1 Antigen 0
CD274 protein, human 0
Hypoglycemic Agents 0
Immune Checkpoint Inhibitors 0
Nivolumab 31YO63LBSN
Metformin 9100L32L2N

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

1487-1493

Informations de copyright

Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Chiara Ciccarese (C)

Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Università Cattolica del Sacro Cuore, Rome, Italy.

Roberto Iacovelli (R)

Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; roberto.iacovelli@policlinicogemelli.it.

Sebastiano Buti (S)

Medical Oncology Unit, University Hospital of Parma, Parma, Italy.

Francesca Primi (F)

Department of Medical Oncology, Belcolle Hospital of Viterbo, Viterbo, Italy.

Serena Astore (S)

Università Cattolica del Sacro Cuore, Rome, Italy.

Francesco Massari (F)

Department of Medical Oncology, Sant'Orsola-Malpighi Hospital, Bologna, Italy.

Miriam Grazia Ferrara (MG)

Università Cattolica del Sacro Cuore, Rome, Italy.

Giuseppe Palermo (G)

Department of Urology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Nazario Foschi (N)

Department of Urology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Valerio Iacovelli (V)

Department of Urology, San Carlo di Nancy Hospital, Rome, Italy.

Ernesto Rossi (E)

Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Giovanni Schinzari (G)

Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Università Cattolica del Sacro Cuore, Rome, Italy.

Pierluigi Bove (P)

Department of Urology, San Carlo di Nancy Hospital, Rome, Italy.

Pierfrancesco Bassi (P)

Department of Medical Oncology, Sant'Orsola-Malpighi Hospital, Bologna, Italy.

Emilio Bria (E)

Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Università Cattolica del Sacro Cuore, Rome, Italy.

Giampaolo Tortora (G)

Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Università Cattolica del Sacro Cuore, Rome, Italy.

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Classifications MeSH