Wednesday was the first full day of sessions at the 2015 San Antonio Breast Cancer Symposium. Talks focused on advances in immunotherapy, drug resistance, tumor biology and biomarkers. Here are a few highlights from the podium talks.
Advances in Antibody Therapies
Using data from the JAVELIN trial, Dr. Luc Dirix of Sint-Augustinus Hospital, Belgium examined the use of avelumab, a PD-L1-targeted immunotherapy, in patients with locally advanced or metastatic breast cancer.
While response to the treatment was modest in the patient group as a whole, patients with triple negative breast cancer (TNBC) whose tumors expressed the PD-L1 protein were particularly responsive to the anti-PD-L1 therapy. Anti-PD/PD-L1 drugs are targeted cancer immunotherapies that work by blocking the immunosuppressive actions of tumor cells.
“This speaks to how difficult it is to do these trials,” said Dr. Peter Ravdin of the University of Texas Health Science Center in an advocate session hosted by Alamo Breast Cancer Foundation Wednesday. He likened these results to the early trastuzumab (Herceptin) trials and emphasized the importance of selecting the right patients when testing targeted therapies.
“You need to have a target that you can hit effectively, but you also need to identify people who have that target,” he added.
Estrogen Receptor Mutations and Outcomes
Mutations in the estrogen receptor gene (ESR1) are associated with the development of resistance to endocrine (anti-hormone) therapies in advanced ER-positive breast cancer.
In an analysis that measured tumor DNA in blood samples from patients on the BOLERO-2 trial, BCRF investigator, Dr. Sarat Chandarlapaty and colleagues found that specific mutations in the estrogen receptor called D538G and Y537S were more common in patients with advanced, ER-positive breast cancer than was previously observed. BOLERO-2 was a randomized clinical trial in which patients received the aromatase inhibitor exemestane alone or with everolimus. Patients with the ESR1 mutations did not respond as well to the therapies as those who do not have these mutations. Read more about Dr. Chandarlapaty’s study here.
Reducing Side Effects Induced by Targeted Therapies
While targeted therapies have fewer systemic toxicities than standard chemotherapies, they are not without side effects that can limit their use for some women. For instance, aromatase inhibitors (AIs) that target estrogen production can cause bone loss similar to osteoporosis. Traztuzumab (Herceptin®), a drug that blocks the HER2 protein, may increase the risk of cardiac events.
On Wednesday at SABCS, scientists revealed they may have found a way to prevent these side effects by combining existing drugs used to prevent these diseases with cancer therapies.
Previous studies have shown a clear benefit of bisphosphonates (used to prevent osteoporosis) not only in reducing AI-induced bone loss but also in improved survival. Dr. Michael Gant of the Medical University in Vienna presented data from the Austrian Breast and Colorectal Cancer Study Group on the impact of an osteoporosis-inhibiting drug called denosumab on survival in post-menopausal women receiving AI therapy. In a cohort of 3,425 women, Dr. Gant and colleagues found that women receiving denosumab had an 18 percent relative improvement in survival compared to women receiving AI therapy alone.
Dr. Edith Pituskin from the University of Alberta discussed the findings of MANTICORE, a Canadian study, designed to determine if drugs used to prevent cardiac disease, specifically, ACE inhibitors and beta blockers, could reduce the cardiotoxicity associated with traztuzumab in patients with early stage HER2 positive breast cancer.
In this randomized trial of 99 patients, those who were given beta blockers with traztuzumab had fewer cardiac complications. While the study was not definitive in the prevention of traztuzumab- related cardiac events, it did show that the addition of the s/b anti-cardiac drugs was safe and well tolerated.
In addition to the many research updates throughout the day, three award lectures were presented during Wednesday’s sessions. BCRF congratulates its investigators Drs. Norman Wolmark , Myles Brown and Martine Piccart for the recognition of their contributions in advancing breast cancer care. Read more here.
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