The METTEN study assessed the efficacy, tolerability, and safety of adding metformin to neoadjuvant chemotherapy plus trastuzumab in early HER2-positive breast cancer (BC). Women with primary, non-metastatic HER2-positive BC were randomized (1:1) to receive metformin (850 mg twice-daily) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of 3-weekly FE75C plus trastuzumab (arm A), or equivalent regimen without metformin (arm B), followed by surgery. Primary endpoint was the rate of pathological complete response (pCR) in the per-protocol efficacy population. pCR rate was numerically higher in the metformin-containing arm A (19 of 29 patients [65.5%, 95% CI: 47.3–80.1]) than in arm B (17 of 29 patients [58.6%, 95% CI: 40.7–74.5]; OR 1.34 [95% CI: 0.46–3.89], P = 0.589). The rate of breast-conserving surgery was 79.3% and 58.6% in arm A and B (P = 0.089), respectively. Blood metformin concentrations (6.2 μmol/L, 95% CI: 3.6–8.8) were within the therapeutic range. Seventy-six percent of patients completed the metformin-containing regimen; 13% of patients in arm A dropped out because of metformin-related gastrointestinal symptoms. The most common adverse events (AEs) of grade ≥3 were neutropenia in both arms and diarrhea in arm A. None of the serious AEs was deemed to be metformin-related. Addition of anti-diabetic doses of metformin to a complex neoadjuvant regimen was well tolerated and safe. Because the study was underpowered relative to its primary endpoint, the efficacy data should be interpreted with caution.

BackgroundLocally advanced head and neck squamous cell carcinoma (LAHNSCC) is a heterogeneous disease in which better predictive and prognostic factors are needed. Apart from TNM stage, both systemic inflammation and poor nutritional status have a negative impact on survival.MethodsWe retrospectively analysed two independent cohorts of a total of 145 patients with LAHNSCC treated with induction chemotherapy followed by concurrent chemoradiotherapy at two different academic institutions. Full clinical data, including the Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio and derived neutrophil to lymphocyte ratio, were analysed in a training cohort of 50 patients. Receiver operating characteristic curve analysis was used to establish optimal cut-off. Univariate and multivariate analyses of prognostic factors for overall survival (OS) were performed. Independent predictors of OS identified in multivariate analysis were confirmed in a validation cohort of 95 patients.ResultsIn the univariate analysis, low PNI (PNI<45) (p=0.001), large primary tumour (T4) (p=0.044) and advanced lymph node disease (N2b-N3) (p=0.025) were significantly associated with poorer OS in the validation cohort. The independent prognostic factors in the multivariate analysis for OS identified in the training cohort were dRNL (p=0.030) and PNI (p=0.042). In the validation cohort, only the PNI remained as independent prognostic factor (p=0.007).ConclusionsPNI is a readily available, independent prognostic biomarker for OS in LAHNSCC. Adding PNI to tumour staging could improve individual risk stratification of patients with LAHNSCC in future clinical trials.

Background: Consumption of fibre-enriched orange juice may be an appropriate way to supplement daily fibre intake and achieve beneficial effects on metabolic health. The present study aimed to assess the short-term effects of fibre-enriched orange juice on postprandial metabolism and satiety in a healthy adult population. Methods: In this double-blind, randomised, placebo-controlled, crossover study 10 healthy subjects underwent two one-day trials in which they consumed an orange juice beverage containing 1.4 g/100 mL of citrus fibre (29.3% soluble and 41.9% insoluble) or a placebo (regular orange juice without added fibre). Postprandial glucose, insulin, gut hormones (GLP1, GIP and ghrelin), leptin and qualitative appetite/satiety assessment were measured every 15 or 30 min over the 120 min test period. Results: The fibre-enriched orange juice decreased postprandial serum glucose and circulating insulin levels at 15 min compared with the placebo. In addition, after intake of the fibre-enriched juice, a significant effect on qualitative feelings of satiety and fullness was observed at 15 and 120 min, and was accompanied by a significant decrease in GLP1 response at 15 min. No significant changes were observed in leptin, GIP and ghrelin after juice intake. Conclusions: In healthy individuals, a single acute consumption of fibre-enriched orange juice has short-term beneficial effects on postprandial glycaemia, circulating insulin levels and satiety through GLP1 secretion.