The Challenges, Achievements and Future Directions for the Combinations Alliance

By Mark Saunders, Manchester ECMC

The global burden of cancer continues to rise largely because of aging and population growth together with an increase in cancer-causing behaviours such as smoking, in economically developing countries. In 2008 there were nearly thirteen million new cases of cancer and almost eight million cancer deaths. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, whilst lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. A substantial proportion of these cases could be prevented, by implementing programs for tobacco control, increasing vaccination rates, public health campaigns promoting a healthier lifestyle and early detection. However, until these bear fruit, the treatment of cancers with surgery, radiotherapy and chemotherapy are the mainstay of our attack.

In the “past” agents were developed and then simply combined to try to combat emerging resistance and to limit over-lapping toxicities. This was a “non-scientific” way of tackling the problem but was the best available in that era. Advances were made, but progress was slow, expensive and involved the cooperation of millions of patients. Simply adding novel agents to current therapies without knowing how they work is an expensive way of getting a negative result! We have to become cleverer. We need to determine the genetic or biological profile of a cancer and develop agents or combinations to tackle this problem.

The Combinations Alliance was formed back in 2010 with the aim of working with companies and using the expertise of the ECMC to generate more scientifically led novel combination trials for patients in the UK. AstraZeneca were the first company to collaborate in the proposed business model, providing large-scale access to their development pipeline and financial support to run the studies. This led to a series of workshops to showcase their drugs and to present the proposals put forward by the different researchers. Over the last four years five meetings were held and over 90 expressions of interest (EOIs) were proposed. From these a total of 14 have been submitted to the New Agents Committee (NAC) and 12 were successful (86% success rate) plus another two later adopted by the Alliance (VANSEL and DREAM). Over this period of time we have seen improved quality of study proposals and increased levels of collaboration. We are delighted that Lilly have now come on board and have allowed access to a Hedgehog inhibitor.

What I think the Combinations Alliance has achieved is to facilitate the collaboration between different investigators, from different ECMCs and to increase the dialogue with different companies. It has been a success by the very fact that trials have been funded, started, recruited and been completed. Where do you go from here? I think that it has been a learning experience and we are better at selecting trials that are more likely to be a success. Now that two companies are involved it is hoped that others will “bite the bullet” and allow access to their drugs. In turn, the Combinations Alliance will facilitate their access to the ECMCs in an efficient and cost-effective manner. It may also provide the platform for different companies to collaborate and combine their agents that have scientific rationale for a positive interaction in a particular tumour site. It is possible that in a few years time, if the momentum continues, that workshops will be held showcasing drugs from a series of different companies leading to collaborative trials from various ECMCs evaluating drug combinations from different pharmaceutical companies. This will be a great leap forward compared to the “past”.