1000P - Metformin plus paclitaxel for metastatic or recurrent head and neck cancer: final results of the randomised prospective METTAX trial (NCT01333852)

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cytotoxic agents
Head and Neck Cancers
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological therapy
Presenter Lucas Dos Santos
Citation Annals of Oncology (2014) 25 (suppl_4): iv340-iv356. 10.1093/annonc/mdu340
Authors L.V. Dos Santos1, L.D.S. Viana2, J.P. Lima3, L.T. Feltrin2, C. Scapulatempo4, A.L. Carvalho5, J.B.C. Carvalheira6
  • 1Internal Medicine, University of Campinas, 02402100 - sao paulo/BR
  • 2Medical Oncology, Hospital De Cancer De Barretos, Barretos/BR
  • 3Medical Oncology, The Royal Marsden Hospital, London/GB
  • 4Pathology And Cpom - Molecular Oncology Research Center, Hospital De Cancer De Barretos, Barretos/BR
  • 5Head And Neck Surgery, Hospital De Cancer De Barretos, Barretos/BR
  • 6Internal Medicine, University of Campinas, sao paulo/BR

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Abstract

Aim

Background: Metformin, the most common anti-diabetic drug worldwide, has shown anticancer properties as single agent and synergistic effect with taxanes in preclinical models. This study evaluated the combination of paclitaxel and metformin for platinum-refractory recurrent or metastatic head and neck cancer.

Methods

Patients (ECOG 0-2) were randomised in a 1:1 ratio to paclitaxel 175mg/m2 every 21 days plus placebo or metformin (1500-2500mg daily) until disease progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS) at week 12. Secondary end-points were PFS, overall response rate (ORR), overall survival (OS) and safety.

Results

Between February 2011 and January 2013, 45 patients were randomised, and three were further excluded due to protocol violations (paclitaxel plus placebo N = 22; paclitaxel plus metformin N = 20). The study was closed prematurely due to low accrual. PFS at week 12 were 31.8% and 50% for placebo and metformin, respectively (p = 0.23). Median PFS was 64 days for placebo and 80 days for metformin - stratified-p = 0.124. The addition of metformin reduced the risk of progression or death by 30% (HR 0.70 - 95%CI 0.38-1.31, p = 0.266). The study arm, performance status and age were strong prognostic factors for PFS in multivariate analysis. In multivariate analysis, metformin reduced the risk of progression or death by 52% (HR 0.48 95% CI 0.24-0.97, p = 0.040). OS was not different between placebo and metformin groups. Only performance status and age were prognostic for OS in the multivariate analysis. ORR were 4.5 and 10% for placebo and metformin arm, respectively (p = 0.49). Overall, both treatments were well tolerated. Patients in metformin arm experienced more diarrhoea and weight loss, all grades 1-2. Grade 3-5 adverse events were not different between placebo and metformin (45.5 and 50%, p = 0.76). In general, adverse events were manageable, notably diarrhoea.

Conclusions

This is the first report of a randomised trial evaluating metformin as anticancer agent. Metformin improved PFS in this population. Further investigation as single agent or combination in head and neck and other cancers is needed.

Disclosure

All authors have declared no conflicts of interest.