A Breakthrough Treatment Passes the Test of Time

The drug trastuzumab – known by brand names including Herceptin– is an inspiring success story in the treatment of breast cancer. Developed in the 1990s, it has saved the lives of countless women with early-stage HER2-positive disease.

But the development of all drugs raises questions: will today’s breakthrough be as effective tomorrow? Are there long-term risks to patients? Can everyone, including governments making important funding decisions, have total faith in this treatment?

These are questions Associate Professor Nicholas Wilcken, Director of Medical Oncology at Westmead and an international research team addressed in their meta-analysis of seven randomised trials from the early 2000s for a study published in The Lancet Oncology in 2021. They reviewed data from more than 13,000 women as well as rich follow-up information generated since.

Their findings, while no surprise, are an essential and powerful vote of confidence: adding trastuzumab to a chemotherapy regimen for early-stage HER2-positive cancer reduces the death rate and recurrence by a third. Concerns that the drug, associated with heart damage, might do more harm than good are not supported by evidence.

“You could say that this study is the definitive word on the effectiveness and safety of what 20 years ago was an exciting new drug,” Associate Professor Wilcken says. “It was important to clarify that all of the trials broadly show the same thing, that there wasn’t a lot of fall off in results over time; trastuzumab is the real deal.”

The HER2 protein exists in everyone, but research in the 1980s and 90s showed that its presence in increased numbers on the surface of breast cancer cells was particularly deadly. Women affected were more likely to die from the disease and, after surgery and if treated with chemotherapy, the tumours more likely to recur. But US researcher Dr Dennis Slamon developed an antibody – trastuzumab – that blocked the receptor and halted cancer cell growth. Promising lab results quickly progressed to large clinical trials and the impact was powerful.

“Drug-wise, this is one of three or four total gamechangers in breast cancer treatment,” says Associate Professor Wilcken. “Trastuzumab has markedly improved survival from HER2-positive breast cancer, roughly halving the risk of it coming back after surgery and reducing the chances of dying of cancer by a third.

“With this study, we’ve drawn a line under it to say that it is as proven as anything could be in medicine, which allows you to move on and ask the next question.”

Publication

Early Breast Cancer Trialists’ Collaborative group (EBCTCG). Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials. Lancet Oncol. 2021 Aug;22(8):1139-1150. doi: 10.1016/S1470-2045(21)00288-6. PMID: 34339645; PMCID: PMC8324484.