Adjuvant chemotherapy no benefit in patients with rectal cancer

Abstract

130 British Journal of Hospital Medicine, March 2011, Vol 72, No 3 New data from the randomized, double-blind, placebo-controlled, multicentre phase III RADIANT-2 trial has revealed that combination therapy with a rapamycinderived immunosuppressant, everolimus, and the somastatin analogue, octreotide LAR, lengthens median progressionfree survival in patients with advanced neuroendocrine tumours. Dr James Yao, Associate Professor, MD Anderson Cancer Centre, University of Texas, Houston, Texas, reported that patients who received the everolimus–octreotide LAR combination had a median progression-free survival of 16.4 months vs 11.3 months in patients assigned to placebo plus octreotide LAR. ‘Conventional chemotherapy has limited efficacy for patients with advanced neuroendocrine tumours, and there remains a significant unmet medical need in this population,’ he commented. While the everolimus and octreotide LAR combination did not achieve its primary progression-free survival end point, the 5.1-month increase in progression-free survival is a clinically meaningful improvement. Importantly, analyses that adjusted for imbalances in baseline characteristics in the two treatment groups and inconsistencies in the review of radiology scans for disease progression showed that everolimus plus octreotide LAR significantly decreased the likelihood of disease progression. A total of 429 patients with advanced lowor intermediate-grade neuroendocrine tumours and a history of symptoms attributed to carcinoid syndrome were randomized to treatment with oral everolimus (10 mg/day) plus octreotide LAR (30 mg administered by intramuscular injection every 28 days) or placebo plus octreotide LAR. Treatment continued until disease progression. Dr Yao said that octreotide LAR has been the foundation of therapy for patients with neuroendocrine tumours, but additional treatment options were needed. Everolimus, an oral inhibitor of mTOR, had demonstrated promising antitumour activity in patients with neuroendocrine tumours as a single agent and in combination with octreotide LAR in two phase II studies. The difference in median progression-free survival between the two arms of RADIANT-2 represented a 23% reduction in risk of progression (hazard ratio=0.77, P=0.026). Correcting for the informative censoring bias, further analysis showed a significant 5.5-month improvement in median progression-free survival with the combination treatment (hazard ratio=0.60, P= 0.0014). The benefit of the everolimus–octreotide LAR combination was seen across all patient sub-groups. Most frequent drug-related adverse events were stomatitis, rash, fatigue, and diarrhoea; mostly grade 1–2. Grade 3–4 adverse events reported in >5% were stomatitis, fatigue, diarrhoea, infections and hyperglycaemia. Dr Yao concluded: ‘The combination of everolimus and octreotide LAR provided a 5.1month clinically meaningful increase in median progressionfree survival – a benefit that increased to 5.5 months after correcting for reporting bias.’ Stephen Pinn Success with combination therapy for neuroendocrine cancer asCO GastrOintestinal CanCers sympOsium san FranCisCO, CaliFOrnia, 20–22 January