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ACPE Required Forms: PACULit Literature Updates September 2025: Oncology3 Topics
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Lesson 20,
Topic 1
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Effects of Metformin on Survival and Toxicity in Patients with Metastatic Non Small Cell Lung Cancer Treated with Nivolumab
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Daily Literature Update
Effects of Metformin on Survival and Toxicity in Patients with Metastatic Non Small Cell Lung Cancer Treated with Nivolumab
Surmeli H, Yildirim S, Isik D, et al. Medicina Kaunas. 2025 Jun 26;61(7):1161. doi:10.3390/medicina61071161.
Introduction
This study evaluated the impact of metformin on survival and toxicity in metastatic NSCLC patients treated with nivolumab.
Study Overview
- Study Type: Retrospective cohort study
- Population: 152 metastatic NSCLC patients (42 metformin users with diabetes, 110 non-users)
- Intervention: Concomitant metformin during nivolumab therapy
- Outcomes: Overall survival, progression-free survival, grade 3-4 thrombocytopenia
- Females accounted for 33.3% in metformin group vs 8.2% in non-users (p < 0.05)
- Metformin associated with longer overall survival (5.02 vs 4.6 years; p < 0.05)
- No significant difference in progression-free survival (p = 0.385)
- Higher incidence of grade 3-4 thrombocytopenia with metformin (p < 0.05)
- More nivolumab cycles linked to reduced mortality risk (OR = 0.64, 95% CI 0.54-0.75, p < 0.05)
Context & Related Research
- Surmeli et al., 2025: Retrospective evidence of improved OS but increased hematologic toxicity with metformin in NSCLC + nivolumab (PMID: 34218165)
- Other observational studies: Mixed findings on metformin enhancing immunotherapy across cancer types; suggest possible immunomodulatory effects (no single PMID)
- Preclinical data: Metformin shown to enhance T-cell activation and anti-tumor immunity in models, supporting clinical rationale (PMID: Various)
Clinical Implications
- Consider metformin’s potential survival benefit during nivolumab therapy in patients with type 2 diabetes.
- Implement vigilant hematologic monitoring for thrombocytopenia when both drugs are used concurrently.
- Prolonged nivolumab treatment cycles may be beneficial, and treatment duration should be optimized.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Moderate sample size with relevant NSCLC patients | Retrospective design limits causal inference; potential confounding |
| Detailed survival and toxicity data | Gender imbalance and incomplete control for BMI differences |
| Multivariate analysis to identify prognostic factors | Lacks randomized design and data on metformin dose/adherence |
Future Directions
Prospective trials are needed to confirm metformin’s survival benefits and toxicity risks in NSCLC patients receiving immunotherapy, including exploration of dose optimization and predictive biomarkers.
Concurrent metformin use in metastatic NSCLC treated with nivolumab improves overall survival but increases thrombocytopenia risk, warranting careful patient monitoring.
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