A combination of lapatinib and trastuzumab (Herceptin) before surgery shrinks and may even destroy tumours in women with HER2 positive disease within 11 days, according to new research
photo: Julia Sero/the ICR
Breast cancer cells stained for DNA (red), NFkB (green), and a reactive oxygen species probe (blue)
The EPHOS B trial, led by researchers at The Institute of Cancer Research, London, the University of Manchester and University Hospital of South Manchester NHS Foundation Trust, studied 257 women with HER2 positive breast cancer in the short gap between initial diagnosis and surgery to remove their tumours.
In the trial, women were split into three groups and treated for 11 days before their surgery.
Initially, women were randomised to receive either trastuzamab, or lapatinib or no treatment – but halfway through the trial, after evidence emerged from other trials of the effectiveness of the combination, the design was altered so that additional women allocated to the lapatinib group were also prescribed trastuzumab.
The trial set out to study the biological effects of the drug combination by measuring biological markers of cellular proliferation after 11 days of therapy.
But when trying to measure this, the researchers discovered that in roughly a quarter of the 66 women who received both drugs, the remaining tumour was too small for the second measurement of cell proliferation.
17% of the women receiving both drugs had only minimal residual disease – defined as an invasive tumour smaller than 5mm in size – and 11% had a pathological complete response, meaning no biological sign of invasive tumour could be found in the breast.
3% of the women treated with trastuzumab only had residual disease or complete response.
The researchers said that observing a disease response after 11 days was very surprising.
Trial Co-leader Judith Bliss, director of the Cancer Research UK-funded clinical trials and statistics unit at the ICR, said: “It was unexpected to see quite such dramatic responses to the trastuzumab and lapatinib within 11 days.
“Our results are a strong foundation on which to build further trials of combination anti-HER2 therapies prior to surgery – which could reduce the number of women who require subsequent chemotherapy.”
Clinical chief investigator and trial co-leader Nigel Bundred, said: “These early and significant tumour regressions seen on dual anti-HER2 therapy suggest that we will be able to personalise treatment for these cancers on the basis of early response, allowing us to identify patients who in the future may avoid treatment morbidity or avoid chemotherapy”.
Arnie Purushotham, senior clinical adviser at Cancer Research UK, said: “These results are very promising if they stand up in the long run and could be the starting step of finding a new way to treat HER2-positive breast cancers.
“This could mean some women can avoid chemotherapy after their surgery – sparing them the side-effects and giving them a better quality of life.”