Treatment with the HER2-targeted drugs lapatinib and trastuzumab before surgery and chemotherapy led to significant shrinkage or disappearance of the tumors in approximately one-quarter of women with HER2-positive breast cancer. These findings were presented at the 10th European Breast Cancer Conference.1
“This has ground-breaking potential because it allows us to identify a group of patients who, within 11 days, have had their tumors disappear with anti-HER2 therapy alone and who potentially may not require subsequent chemotherapy. This offers the opportunity to tailor treatment for each individual woman,” said Professor Nigel Bundred, MD, FRCS, professor of Surgical Oncology at The University of Manchester and the University Hospital of South Manchester NHS Foundation Trust in the United Kingdom.
This multicenter clinical trial, known as EPHOS-B, recruited 257 women with newly diagnosed, operable, HER2-positive disease between November 2010 and September 2015. In the first part of the trial, 130 women were randomized to receive no preoperative treatment (control group), or trastuzumab (Herceptin) only, or lapatinib (Tyverb) only, for 11 days after diagnosis and before surgery.
However, emerging evidence led to an amendment so that, from August 2013 on, the next 127 women were randomized to the control group, or to receive trastuzumab only, or the combination treatment. For both parts of the trial, the women continued to receive standard of care treatment after surgery.
Samples of tumor tissues were compared from the first biopsy and from surgery. The comparison looked for a drop in the Ki67 protein, an indicator of cell proliferation, or for a rise in apoptosis of 30% or more from the time of the first biopsy.
The second part of the trial indicated that, among women who received the combination treatment, 11% had a pathologic complete response and 17% had minimal residual disease. In contrast, among women who received only trastuzumab, 0% had a pathologic complete response and 3% had minimal residual disease, while none had either response in the control group. The responses in the group that received the combination treatment included women who had presented with stage II disease.
“These results show that we can get an early indication of pathological response within 11 days, in the absence of chemotherapy, in these patients on combination treatment. Most previous trials have only looked at the pathological response after several months of treatment,” said Professor Judith Bliss, MSc, lead researcher from The Institute of Cancer Research, London, United Kingdom, and co-leader of the trial.
“Clearly these results need further confirmation, but I suspect the excitement from seeing the speed of disappearance of the tumors will mean that several trials will attempt to confirm these results.”
So far, EPHOS-B is the only trial that has investigated giving combination treatment alone, without chemotherapy, in the two weeks between diagnosis and routine surgery. Bundred explained that treatment while waiting for surgery has the potential to identify a group of patients whose disease is particularly sensitive to anti-HER2 therapy.
1. Bundred N, Cameron D, Armstrong A, et al. Effects of perioperative lapatinib and trastuzumab, alone and in combination, in early HER2+ breast cancer − the UK EPHOS-B trial (CRUK/08/002). Clinical science symposium presented at: 10th European Breast Cancer Conference; March 9-11, 2016; Amsterdam, The Netherlands. Abstract 6LBA.