Kimberly L. Blackwell, MD
Since its approval in 1998 to treat metastatic breast cancer, the anti-HER2 monoclonal antibody trastuzumab has dramatically expanded life expectancy and improved quality of life for women diagnosed with HER2-positive disease. It remains the standard-of-care, first-line treatment for metastatic breast cancer. In less than a decade, the FDA has added three new drugs to the arsenal to treat advanced HER2-positive disease, while a growing number of clinical studies are evaluating dual-agent approaches to therapy through a variety of drug combinations.
At the MBCC mini-symposium, Kimberly L. Blackwell, MD, the director of the Breast Cancer Program at Duke Cancer Institute, discussed current treatment options in a presentation entitled “Targeting HER2 in Metastatic Breast Cancer in 2014.” She put emerging treatment trends into context during an interview in advance of her talk.How have treatment options and prognoses changed over the past decade for women diagnosed with HER2-positive breast cancer?
We can no longer speak of diagnosing breast cancer in broad terms, but rather of different subtypes of breast cancer and cancer stage. Prognoses, based on a specific cancer’s biology, are very different. But we can say that the prospects for women diagnosed with HER2-positive breast cancer have improved. With certain subtypes, discovered in the early stages of the disease, we can start talking about a cure. This marks a paradigm change; we could not have said this 10 years ago. There are now people with HER2-positive disease who have no recurrence if they are treated earlystage with trastuzumab. The prognosis for these women is pretty tremendous, and it has allowed us to save years and years of life for them.How have prospects changed for women with HER2- positive metastatic disease?
There are a lot of options for these women if their cancer remains HER2-dependent. We now treat metastatic breast cancer as we would a chronic disease, such as diabetes or heart disease, with targeted therapies and combinations of therapies.
A serious challenge we face with some of these women, however, is brain metastases. This is a tragic situation, especially for women who have lived a high-quality life for several years and then develop metastases. It is a difficult cancer to treat, and these patients may also suffer the long-term effects of stroke. We must recognize that we aren’t able to adequately treat progressive brain metastasis.Where are the post-trastuzumab drugs proving most effective, and in what settings?
The approval of T-DM1, an antibody-drug conjugate, is changing the way we care for metastatic breast cancer and solid tumors in general. Treatment that doesn’t hurt the immune system is a major breakthrough that will improve patient care. Lapatinib is not super effective therapeutically. We see that lapatinib and trastuzumab are more effective together than lapatinib alone. But there may be new life for this drug. The data we have now do not look at combinations with T-DM1 or the effect of layering trastuzumab with lapatinib or pertuzumab.What role are dual-agent therapies playing in the treatment of metastatic disease?
We’re doubling down on HER2-positive cancer. There will be few studies from now on that evaluate trastuzumab alone; in metastatic breast cancer, dual agents are here. The dilemma facing clinicians over the next 5 years is going to be sequencing.How do the newer drugs improve upon the performance of trastuzumab?
There is a limited ability to improve upon trastuzumab’s performance with these newer drugs. There are studies whose results we’re anxiously awaiting, but it’s really unclear how useful they will be. With healthcare reform and the cost to society of developing and prescribing new drugs, we need to look very carefully at the value of small incremental gains and to ask some very hard questions as a society: Is it worthwhile to add new medications? How many people need these new expensive therapies?Are there drugs on the horizon that may improve treatment for HER2-positive disease?
Everolimus [approved in HER2-negative settings] may prove valuable. While it showed only a small improvement in progression-free survival in BOLERO-3 (1.2 months), I don’t dismiss it. I think its capacity to cross the blood-brain barrier is important and it may prove useful in addressing brain metastases. I think we will also see neratinib come to the table. We saw in the I-SPY 2 study of neratinib in the neoadjuvant setting that it met its primary endpoint. I think that studies of PI3-kinase inhibitors are also going to yield some interesting results.What role do you see for a vaccine?