Our guest blogger, Thomas Fletcher of 'Why Science isn't Boring', looks at a recent Lancet paper - Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial

Cancer is one of the leading causes of death in the UK today, and nearly a quarter of cases are breast cancer. Ensuring effective treatment for breast cancer is therefore an important challenge for healthcare services worldwide. However, these services, such as the NHS, also need to ensure that they are being cost effective with their resources and that any newly proposed treatment will be better than what is already in place. So how do we trial new cancer treatments to ensure they work better than what we already have?

A new paper published by The Lancet has looked at whether a combination of drugs is more effective in treating breast cancer than the individual drugs on their own. They focused on HER2- positive breast cancer, which affects 20% of breast cancer patients and tends not to be as easy to treat. Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that is involved in mediating cell growth and proliferation and that is amplified and over-expressed in this form of cancer. The study used two drugs: Trastuzumab (herceptin), a monoclonal antibody that inhibits HER2 signalling pathways, and Lapatinib (Tykerb), a tyrosine kinase receptor inhibitor that blocks the receptor’s ATP binding- site, preventing self- phosphorylation. Individually both of these drugs have some effect on HER2- positive cancer and are used in treatment, but this study set out to find whether a combination of both would work even better than each drug alone.

This clinical trial is a phase III trial, which are usually large scale trials that confirm a treatment’s efficacy before it is approved by regulatory agencies.  In terms of cancer treatment they are often used to compare the new treatment with existing standards of care. This trial was also open- label, meaning that both the participants and researchers knew which drug was being given to each trial participant (the opposite of a double-blind trial). Since we want all the participants to be treated effectively there is no need to cover up which drugs they are receiving.

Participants were split into three groups, one receiving both drugs simultaneously, and the other two receiving trastuzumab and lapatinib individually.  No placebo was used since the objective of the trial was to compare the treatments, not to confirm the efficacy of new drugs. The clinical objective of the trial was to assess the tumour’s response to treatment.

More patients who received both trastuzumab and lapatinib showed a positive response (51.3%) compared to trastuzumab alone (29.5%), and statistical analysis shows this to be significant (p= 0.0001).The trial has therefore given us ground to believe that drug combination could be a more effective treatment for HER2- positive breast cancer than our current standards of treatment.

While more research will confirm the efficacy, this trial has suggested a new treatment to be more effective than current standards of care. Given the level of improvement in the patients’ condition it would seem plausible that this treatment could be adopted in the near future.

Thomas Fletcher