JAMA sub-issue: Whether metformin can "assist" lung cancer treatment, the key may be this indicator!

▎WuXi AppTec Content Team Editor Currently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become the standard first-line treatment recommendation for EGFR mutation-positive advanced lung adenocarcinoma
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Some previous studies have shown that the traditional type 2 diabetes drug metformin may act as a "partner" of EGFR-TKIs and play a synergistic role in the treatment of lung cancer.
Contradictory conclusions have been drawn, so the use of metformin in the treatment of lung cancer has also been controversial
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Recently, an expert research team from the Spanish National Cancer Institute (Instituto Nacional de Cancerología) published a paper in JAMA Oncology, the world's top journal in the field of clinical oncology, and pointed out that whether metformin can synergize with EGFR -TKIs play an anti-lung cancer effect, which may be closely related to the patient's body mass index (BMI)! Screenshot source: Some experts from JAMA Oncology believe that the inconsistent results of previous clinical trials of EGFR-TKIs and metformin combination regimens may be related to a variety of factors, such as different patient baseline characteristics (such as the occurrence of brain metastases), genetic factors, Metformin dosage and study design
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Among these different factors, whether the benefit of metformin treatment depends on BMI has not been fully evaluated
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The current research team emphasizes that previous results suggest that metformin appears to have beneficial effects only in cancer patients with higher BMI, so it is particularly important to assess the impact of BMI as a parameter on efficacy
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We performed a secondary analysis of data from a published prospective, randomized phase 2 clinical trial (NCT03071705)
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The trial included patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) and randomly assigned to receive EGFR-TKIs alone or the combination of EGFR-TKIs and metformin (500 mg twice daily)
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In the secondary analysis, the median BMI (24) of the trial patients was used as the cutoff value, and the patients were divided into a high BMI group (≥24) and a low BMI group (<24)
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Overall, a total of 133 patients (mean age, 59.
39 years; 64.
7% female) had complete information and were included in the analysis
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The progression-free survival (PFS) time of patients was 10.
54 (95%CI, 8.
92-12.
17) months
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The analysis showed that in patients with BMI ≥24 (n=70; 52.
6%), EGFR-TKIs combined with metformin improved PFS compared with EGFR-TKIs alone (15.
83 months vs 8.
34 months; HR =0.
47 [95% CI, 0.
28-0.
78]; P=0.
003), and this PFS benefit was independent of other factors
.

▲ For NSCLC patients with BMI ≥ 24, the combination regimen improves PFS (Image source: Reference [1]) Not only that, in patients with BMI ≥ 24, EGFR-TKIs combined with metformin treatment compared with patients receiving EGFR-TKIs alone.
There was a significant difference in (OS), 31.
44 months and 18.
00 months, respectively (P=0.
04), and the combined use of metformin was independently associated with the prolongation of OS in these patients (HR=0.
55; 95%CI: 0.
31-0.
98; P=0.
04 )
.

▲ For NSCLC patients with BMI ≥ 24, the combination regimen significantly improved OS (Image source: Reference [1]) At the same time, similar results were not observed in patients with BMI < 24 (n=63; 47.
4%) , EGFR-TKIs combined with metformin therapy compared with EGFR-TKIs alone, the patients' PFS was 7.
88 months and 10.
31 months, respectively (P=0.
65)
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Similarly, EGFR-TKIs combined with metformin regimen did not improve OS compared with EGFR-TKIs alone (20.
46 months vs 27.
99 months; P=0.
68)
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Overall, the results of the current secondary analysis suggest that in patients with EGFR-positive NSCLC with higher BMI, the addition of metformin to EGFR-TKIs may result in a significant PFS benefit as well as a significant OS benefit
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The reason for the contradictory results of previous studies may lie in the different ethnic groups included in different studies, and there may be large differences in the baseline BMI of patients
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The researchers emphasized that the specific mechanism may be that patients with higher BMI are more sensitive to the antitumor effects of metformin, so the clinical benefit of metformin may also be more limited to this specific population
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However, the conclusions of the current study still need to be confirmed by further prospective studies
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Related reading Wu Yilong and Zhou Caicun lead! For the benefit of Chinese patients with non-small cell lung cancer, two new immunotherapy drugs were published in The Lancet-Oncology! JCO heavyweight: Lung cancer patients who have never smoked have more opportunities for targeted therapy! "Nature" sub-issue: Why do some people get lung cancer even if they don't smoke? Where do cancer cells come from? Five types of strategies, ten blockbuster research! Yale Cancer Center: How to choose first-line immunotherapy for driver gene-negative NSCLC? Immunotherapy prolongs "cancer-free survival", a breakthrough in adjuvant therapy for non-small cell lung cancer! The Lancet published landmark research references[1] Arrieta, Oscar, et al.
"Association of BMI With Benefit of Metformin Plus Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors in Patients With Advanced Lung Adenocarcinoma: A Secondary Analysis of a Phase 2 Randomized Clinical Trial.
" JAMA oncology (2022).
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For guidance on treatment options, please visit a regular hospital
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