TAXOMET: A French prospective multicenter randomized controlled phase II study comparing docetaxel plus metformin versus docetaxel plus placebo in mCRPC.

Abstract

5004 Background: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective cohort studies suggest a decrease in PC incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in PC preclinical models, with increase apoptosis when added to DOCE. The addition of MET could enhance DOCE efficacy in mCRPC patients (pts). Methods: TAXOMET is a phase II prospective multicentric randomized controlled trial. Non-diabetic mCRPC pts were assigned 1:1 to receive DOCE 75mg/m2 every 21 days + prednisone (P) 5 mg twice a day and either MET 850mg twice a day (arm A) or placebo (arm B), up to 10 cycles. The primary end point was PSA response rate (≥50% decrease). Main secondary endpoints included objective response rate (ORR, according to RECIST v1.1), clinical and biological progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL). Comparisons between arm A and B were performed using Chi² test for qualitative data and Log-rank test for survival data. Results: From January 2013 to December 2015, 99 pts were randomized (50 pts in arm A and 49 pts in arm B) in 10 french centers, and 95 pts were evaluable. No difference was observed between arm A and arm B in PSA-response rate (72% in both arms), ORR (28% in both arms), clinical or biological mPFS (7.3 months vs 5.8 months p = 0.848) and mOS (24.2 months (95CI: 17.2 – 33.7) vs 19.7 months (95CI: 14.8 – 36.8), p = 0.53), respectively. There was no difference between arms in adverse events, except a trend for diarrhea to be more common with MET (70% in arm A vs 50% in arm B, p = 0.072), but few grade 3-4 events. There was no difference in QoL according to QLQ-C30 score between the two arms during the treatment period. Conclusions: This is the first prospective randomized controlled trial to evaluate the combination of MET with DOCE+P in mCRPC. The addition of MET has no meaningful clinical benefit in this setting. Clinical trial information: NCT01796028.

Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302

“…To date, there has been only one reported randomised trial examining the use of metformin in mCRPC, the phase II TAXOMET study in which 99 patients with mCRPC were randomised to treatment with docetaxel plus metformin versus docetaxel alone in order to increase the estimated PSA-RR from 45 to 60%. No differences in the primary end-point of PSA response rate was seen [ 15 ] and the median OS was 24.2 months (95% CI 17.2–33.7) in the combination arm versus 19.7 months (95% CI 14.8–36.8) with docetaxel alone, which did not meet statistical significance [ 15 ]. A small phase II pilot study of 25 men with mCRPC demonstrated that the addition of metformin after PSA progression on abiraterone did not affect further progression and had no meaningful clinical benefit [ 16 ].…”

Statin and metformin use and outcomes in patients with castration-resistant prostate cancer treated with enzalutamide: A meta-analysis of AFFIRM, PREVAIL and PROSPER

“…In the SAKK 08/09 study using metformin as monotherapy, only 2/44 patients had a PSA 50 response. In the recently presented TAXOMET study, 99 patients with mCRPC who were non-diabetic were randomised between standard docetaxel and prednisone and the addition of metformin (850 mg twice daily); no statistical differences were detected in this small study with limited duration of metformin in any clinically meaningful end-point [ 20 ]. One-third of the patients remained progression free at 12 weeks posttreatment with metformin and the PSA doubling time was prolonged in half of the patients [ 21 ].…”