Analysis of NCT00268476 clinical trial results. Metformin may improve cancer outcomes and survival in high volume mHSPC patients.

[Graham49]

Metformin does not improve survival in unselected metastatic patients but may improve cancer outcomes and survival in high volume patients. Metabolic parameters were significantly improved overall.

LBA70 Adding metformin to androgen deprivation therapy (ADT) for patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC): Overall survival (OS) results from the multi-arm, multi-stage randomised platform trial STAMPEDE

S. Gillessen1 ∙ L.R. Murphy2 ∙ N.D. James3 ∙ … ∙ M.K. Parmar14 ∙ L.C. Brown2 ∙ N. Clarke15 … Show more

DOI: 10.1016/j.annonc.2024.08.2313

“Methods

Non-diabetic pts with mHSPC were randomly allocated 1:1 to standard of care (SOC) or SOC+metformin within STAMPEDE. SOC included ADT ± radiotherapy ± docetaxel ± androgen receptor pathway inhibitor (ARPI). The primary outcome was OS. Target hazard ratio (HR) 0.8 (92% power, 2.5% 1-sided significance). 7 subgroup analyses were pre-specified but not pre-powered.”

“Results

1874 pts with mHSPC were randomised Sep2016-Mar2023. Arms were well balanced: median age 69 years, IQR 63-73; median PSA 84ng/ml, IQR 24-352; de novo 1758 (94%) vs relapsed 116 (6%). Planned SOC included 82% Docetaxel and 3% ARPI. After a median follow-up of 60 months, the HR for OS between arms was 0.91 (p=0.148; 95% CI 0.80-1.03). The median (95%CI) OS was 63 (58-69) and 69 (63-73) months in the SOC and SOC+metformin arms respectively. In patients with high versus low volume disease (CHAARTED def), HR was 0.79 (p=0.006; 0.66-0.93) and 1.0 (p=0.992; 0.79-1.26) respectively. The interaction p-value = 0.086. For progression-free survival:

Overall HR was 0.92 (p=0.164; 0.81-1.04) with HRs of 0.76 (p=0.001; 0.64-0.89) and 1.10 (p=0.401; 0.88-1.37) in the high and low volume subgroups respectively, interaction p-value = 0.006. Metabolic parameters that improved significantly with metformin included reduced weight gain, fasting glucose, HbA1c and total and LDL cholesterol. Fewer patients developed a metabolic syndrome. Adverse events (AE) ≥grade 3 were reported in 52% and 57% in the SOC and SOC+metformin arms, respectively; Gastrointestinal AEs increased with metformin.”

“Conclusions

Metformin does not improve survival in unselected metastatic patients but may improve cancer outcomes and survival in high volume patients. Metabolic parameters were significantly improved overall.”

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[DrawingSnowmen]

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>Regarding baseline characteristics, “Importantly, [83% of patients in arm A and 82% of patients in arm K] had ADT plus docetaxel as their standard of care. Only very few patients had an [androgen receptor pathway inhibitor],” Gillessen said.

>Most metabolic parameters improved significantly with metformin, irrespective of disease volume, which may translate to reduced cardiovascular deaths in the future. Further research is warranted for patients treated with ADT-[androgen receptor pathway inhibitor] doublet backbone because we know that these patients have even more metabolic adverse events,” Gillessen concluded.