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 | Anticancer 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
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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.