Howard A. “Skip” Burris, MD
Recent pivotal breast cancer data presented at the 2018 San Antonio Breast Cancer Symposium (SABCS), particularly with immunotherapy, are just the start of promising directions for researchers, said Howard A. “Skip” Burris, MD.
An updated biomarker analysis from the phase III IMpassion130 trial—data from which were initially presented at the 2018 ESMO Congress—showed that progression-free and overall survival (OS) improvements with the combination of atezolizumab (Tecentriq) and nab-paclitaxel (Abraxane) in patients with metastatic triple-negative breast cancer (TNBC) or inoperable locally advanced TNBC were exclusive to those patients with PD-L1 expression ≥1% on immune cells.
Other biomarkers, which included PD-L1 expression on tumor cells, intratumoral CD8-positive T cells, stromal tumor-infiltrating lymphocytes, and BRCA1/2 mutation status, also confirmed the importance of PD-L1 expression on immune cells in predicting clinical benefit derived from the atezolizumab combination.
Based on the initial IMpassion130 findings, the FDA granted a priority review designation to a supplemental biologics license application for the frontline atezolizumab combination for patients with unresectable locally advanced or metastatic PD-L1–positive TNBC. The initial data showed that there was a 38% reduction win the risk of progression or death with atezolizumab plus nab-paclitaxel versus nab-paclitaxel alone in this patient population. Under the Prescription Drug User Fee Act, the FDA is scheduled to decide on the application by March 12, 2019.
“The data are changing so quickly, it’s difficult to keep up, and folks are certainly interested in seeing how the disease-specific experts are applying this information in their practices,” said Burris.
Looking ahead, Burris said the breast cancer community should expect a focus on molecular profiling as well as upfront testing with PARP and CDK4/6 inhibitors.
In an interview during the 2019 OncLive® State of the Science Summit™ on Breast Cancer, Burris, chief medical officer of Sarah Cannon Research Institute, and president-elect of ASCO, highlighted some of the exciting updates from the 2018 SABCS and what can be expected in the breast cancer field in the year ahead.
OncLive: Reflecting on the recent breast cancer advances, how are these pivotal data informing treatment decisions?
Burris: The data coming out of SABCS and the conversations [at the State of the Science Summit™] were different than prior years, because we have exciting affirmation in all the various subtypes, as well as the various stages of breast cancer. We have promising and almost practice-changing data in HER2-positive breast cancer, TNBC, and in the realm of the estrogen receptor (ER)–positive breast cancer. It was fascinating to see, in one of the presentations at SABCS this year, a wonderful case-based discussion where Dr Cliff Hudis of ASCO moderated and Dr Hal Burstein of Dana-Farber Cancer Institute and Dr Dan Hayes of University of Michigan—all breast cancer experts—debated the strategy.
I thought what was interesting was how crowded the room was and how thirsty the audience was for how people were going to apply the new knowledge going forward. [It covered] what to do with molecular profiling, how to do the prognostic assays, and where they might incorporate the treatment.
What practice-changing data in HER2/TNBC did you find were most exciting?
In the HER2-positive breast cancer treatment paradigm, we have, for many years, really liked T-DM1. The antibody-drug conjugate has been well tolerated, active, and a lot of the data in the adjuvant and neoadjuvant settings have been accruing. It’s been hard to sort out when that might emerge.
With the 2018 SABCS, the KATHERINE data, and seeing T-DM1 so positive over trastuzumab (Herceptin) in the [adjuvant] population was a great win. It makes sense to give additional chemotherapy in that setting, and it makes sense to continue trastuzumab-based therapy. That is the idea behind T-DM1: this “smart bomb,” better-tolerated approach of having chemotherapy linked to an active monoclonal antibody, so that is absolutely going to be something that will be quickly adopted, incorporated, and yield even greater outcomes.
On the TNBC front, we had some wins with positive trials with PARP inhibitors in the metastatic setting. We had some wins with positive trials with antibody-drug conjugates. There are a few new ones coming along and, if the immunotherapy store was going to make sense in breast cancer, most people thought it would be in TNBC. The IMpassion130 data, with atezolizumab in combination with nab-paclitaxel were presented—[the findings were originally shown] at the 2018 ESMO Congress, there are a lot of data there.