A combination of Novartis' Afinitor and Pfizer's Aromasin failed to reach statistical significance in a trial’s secondary endpoint of overall survival.

Eagerly-awaited results from the BOLERO-2 trial looking at the mTOR inhibitor Afinitor (everolimus) plus the aromatase inhibitor Aromasin (exemestane) were presented at the European Breast Cancer Conference in Glasgow and proved disappointing. In the study of women with advanced oestrogen receptor-positive breast cancer, median survival was 31 months for the combo versus 26.6 months for those on Aromasin monotherapy.

Previously reported results had shown the primary endpoint of progression-free survival to be clinically meaningful and statistically significant. Slightly fewer patients (10%) in the everolimus arm had received salvage chemotherapy after cancer progression and no new safety concerns were identified.

Presenting the results, Martine Piccart of the Jules Bordet Institute in  Brussels said she hoped ongoing studies would identify breast cancer patients most likely to benefit from mTOR inhibition. However, “so far we have not been very successful,” she added.

Discussing the findings, Harold Burstein at the Dana Farber Cancer Institute in Boston, said that the trial had a "missing third arm". He added that "it would have been very interesting had this trail been designed to see what everolimus by itself might have achieved”.  

Dr Burstein went on to say that UK and Canadian everolimus/exemestane cost effectiveness analyses put the price “at the high upper end of what would conventionally be considered acceptable trade-offs for cost and drug activity".

Synta’s lead agent on track

Meantime, ganetespib, an investigational drug from Synta Pharmaceuticals shows promising anti-tumour activity in patients with metastatic breast cancer, David Cameron, director of cancer services at NHS Lothian, told attendees at the Glasgow meeting.

Ganetespib is a small molecule inhibitor of heat shock protein 90 (Hsp90) which results in the simultaneous disruption of numerous signalling pathways thought to be critical for tumour cell proliferation and survival.

The interim data presented at EBCC were from the ENCHANT-1 trial, a Phase II study. It showed that ganetespib demonstrated highly encouraging single-agent activity in both HER2+ and triple-negative disease, warranting expanded study.