NOTE, original article title: A randomized phase 2 study of bicalutamide with or without metformin for biochemical recurrence in overweight or obese prostate cancer patients (BIMET-1)

Findings demonstrated good tolerability of metformin plus bicalutamide but rates of achieving undetectable PSA at 32 weeks did not improve with this combination. Metformin monotherapy led to modest PSA decreases in 40% of patients after 8 weeks. Metformin, administered alone and in combination with bicalutamide, showed immune modifying impacts, mainly within NK and T cells subsets.

• In retrospective studies, metformin use has been shown to be linked with reduced incidence of prostate cancer and prostate cancer-specific mortality.

• Preclinical studies have suggested additive anticancer impacts of combining metformin and bicalutamide.

• In this open-label, randomized, phase 2 trial, non-diabetic patients (n=29) with biochemically recurrent prostate cancer, a PSADT of 3–9 months, BMI > 25 and normal testosterone were randomized 1:2 to observation for an initial 8 weeks (Arm A) or metformin 1,000 mg twice daily (Arm B); bicalutamide 50 mg/day was added post-8 weeks to both arms.

• The proportion of patients with undetectable PSA did not differ between the 2 arms.

• In 40.0% of patients with metformin monotherapy, modest PSA decreases ranging from 4% to 24% were noted, vs 11.1% in the observation arm.

• Metformin monotherapy decreased PD-1 ⁺ NK cells, and raised NKG2D ⁺ NK cells.

• Greater decreases in PD-1 expressing NK, CD4 ⁺ T, and CD8 ⁺ T-cell subsets were brought about by the combination of metformin and bicalutamide, vs bicalutamide alone.