Can Metformin Improve Outcomes When Added to Chemotherapy in Prostate Cancer?

The addition of metformin to docetaxel and prednisone did not add a meaningful clinical benefit over placebo in patients with metastatic castration-resistant prostate cancer (CRPC), according to the phase II TAXOMET trial.

“Metformin may be an effective chemosensitizer for docetaxel,” said Marc P. Martin, of the Centre Antoine Lacassagne in Nice, France. The anti-diabetic medication has low cost and minimal side effects, and it is known to decrease prostate cancer incidence and improve time to castration resistance and survival in prostate cancer patients who are diabetic. Martin presented results of the study (abstract 5004) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago.

The TAXOMET trial included 99 patients randomized to receive metformin (50 patients) or placebo (49 patients), along with docetaxel and prednisone. All patients had chemo- and metformin-naive metastatic CRPC, and all patients were non-diabetic. The median age was approximately 70 years; the median baseline prostate-specific antigen (PSA) level was 80.3 ng/mL in the metformin group, and 54.5 ng/mL in the placebo group. Eighteen percent of each group had received prior abiraterone, while less than 5% had received prior enzalutamide or other similar medications.

The primary endpoint of PSA response was no different between the groups. The PSA response rate with metformin was 66%, compared with 63% with placebo (P = .94).

Survival outcomes were also similar. The median progression-free survival was 7.4 months with metformin and 5.6 months without it. The median overall survival in the two groups was 24.6 months and 19.7 months, respectively.

There were also few differences with regard to treatment exposure and characteristics, with similar rates of exposure to metformin/placebo, and to docetaxel. Treatment discontinuation was due to maximal clinical benefit in 44% of metformin patients and 37% of placebo patients, followed by disease progression (26% and 33%, respectively), adverse events (16% and 22%, respectively), and other reasons.

Adverse event rates were generally similar, though Martin pointed out a higher rate of diarrhea in the metformin group. There was no hypoglycemia in the trial, and Martin said there were no unexpected adverse events.

“In this setting, metformin didn’t seem to have meaningful clinical benefits,” Martin concluded, adding that it remains to be seen whether prolonged metformin exposure, beyond the point of docetaxel treatment, may offer some advantage. The pending results of the standard-of-care plus metformin arm of the STAMPEDE trial may soon offer a better answer.

“I want to congratulate Dr. Martin and his team of investigators for completing a prospective, randomized, placebo-controlled trial that will impact clinical care, as this data should reduce off-label use of metformin,” said Mary-Ellen Taplin, MD, of the Dana-Farber Cancer Institute in Boston, who discussed the abstract for ASCO. She noted that the rate of grade 1–2 gastrointestinal toxicity was particularly high with metformin in the context of the chemotherapy. “This type of treatment is not innocuous,” she said.