Impact of Addition of Metformin to Abiraterone in Metastatic Castration-Resistant Prostate Cancer Patients With Disease Progressing While Receiving Abiraterone Treatment (MetAb-Pro): Phase 2 Pilot Study.

There is evidence linking metformin to improved prostate cancer-related outcomes.

Twenty-five men with metastatic castration-resistant prostate cancer and prostate-specific antigen (PSA) progression while receiving treatment with abiraterone from 3 Swiss centers were included in this single-arm phase 2 trial between November 2013 and September 2016. Metformin was added to abiraterone continuously at 1000 mg twice daily in uninterrupted 4-week cycles. The primary end point was the absence of disease progression at 12 weeks (PFS12). The Fleming single-stage design was applied. With a 5% significance level and 80% power, 25 patients were required to test PFS12 ≤ 15% (H0) compared to ≥ 35% (H1). Secondary end points included toxicity and safety issues. The study was registered at (NCT01677897).

The primary end point PFS12 was 12% (3 of 25 patients) (95% confidence interval, 3-31). Most patients had PSA progression, almost half had radiographic progression, but only 1 patient had symptomatic progression. Eleven (44%) of 25 patients had grade 1 and 2 patients each grade 2 (8%) or grade 3 (8%) gastrointestinal toxicity (nausea, diarrhea, loss of appetite). One patient discontinued treatment at week 5 because of intolerable grade 3 diarrhea.

The addition of metformin to abiraterone for patients with metastatic castration-resistant prostate cancer and PSA progression while receiving abiraterone therapy does not affect further progression and has no meaningful clinical benefit. A higher-than-expected gastrointestinal toxicity attributed to metformin was observed.

Clinical genitourinary cancer. 2019 Jan 02 [Epub ahead of print]

Michael Mark, Dirk Klingbiel, Ulrich Mey, Ralph Winterhalder, Christian Rothermundt, Silke Gillessen, Roger von Moos, Michael Pollak, Gabriela Manetsch, Räto Strebel, Richard Cathomas

Kantonsspital Graubünden, Chur, Switzerland. Electronic address: ., SAKK CC Bern, Bern, Switzerland., Kantonsspital Graubünden, Chur, Switzerland., Kantonsspital Luzern, Luzern, Switzerland., Kantonsspital St Gallen, St. Gallen, Switzerland., Lady Davis Institute for Medical Research Jewish General Hospital Montreal, Montreal, Canada.