Giuseppe Curigliano, MD PhD, Associate Professor of Medical Oncology at University of Milano and the Head of the Division of Early Drug Development at European Institute of Oncology, Milan, Italy
What are the most practice-changing updates on immunotherapy for breast cancer?
Two sets of data are very practice-changing.
- The first one is related to patients with triple negative metastatic breast cancer in which there is a clear benefit from the combination of atezolizumab plus nab-placlitaxel in patients that over express on the primary tumour PD-L1. In these patients, there is finally a benefit in terms of overall survival and progression-free survival, that’s why this combination has been approved by FDA and EMA for the treatment of first-line triple negative metastatic breast cancer.
- The second comes from the neoadjuvant setting, patients that are candidates for surgery, and before surgery they receive therapeutic treatment. We have Keynote 522, it is an outstanding trial, in which patients with early breast cancer and triple negative disease received standard of care chemotherapy plus or minus pembrolizumab. And, what is impressive is that the additional pembrolizumab increased the rate of pathological complete response (pCR), that is a very important endpoint in the neoadjuvant setting because pCR correlates with the outcome, with the event-free survival. So, pCR increase was from 50% to 64% so it is statistically significant and if I have to predict, I am quite sure pembrolizumab will be approved for the neoadjuvant setting.
- Another important result from the Keynote 522 is that if you look at the data on event-free survival, in terms of appearance of metastases, it’s quite clear that in the arm that received pembrolizumab, they had less events.
How about the adverse events of immunotherapy?
The most common adverse events in both the metastatic setting and neoadjuvant setting is the endocrine adverse event, hypothyroidism, that is close to 15%. So, it is a common toxicity by immune checkpoint inhibitors that usually does not affect dramatically the quality of life of patients. So, you know, in the beginning, in the treatment of melanoma of course, the observation of these endocrine adverse events was an issue. But now, it is not an issue because the benefit is much more than the side effects, but the most common event is hypothyroidism.
What is coming in terms of imaging for follow up of breast cancer in the neoadjuvant setting?
- For now what we are doing is to perform a mammogram, ultrasound, MRI. And usually there is no 100% concordance between imaging and the final result from the surgery.
- But in the future, imaging will be more sophisticated because we have the integration of radiomics, the artificial intelligence that acquires the imaging and this will permit us to identify clusters that help with diagnosis.
- Another thing we’ll have in the future, is the use of liquid biopsy, which is using circulating blood to detect fragments of circulating tumour DNA.
- So, if you are exposed to a treatment and you have clearance of circulating tumour DNA, you have for sure maximal probability to have cured that cancer. So, the future in evaluating the disease in the early disease setting will be in the integration of radiomics and secondly, the use of circulating tumour DNA.