Adam M. Brufsky, MD, PhD
As investigators increase their understanding of the biology of triple-negative breast cancer (TNBC), new approaches are emerging that could optimize patient outcomes.
“There are a lot of interesting data in triple-negative breast cancer, a field where we didn’t really have a lot, until recently,” said Adam M. Brufsky, MD, PhD.
For example, the FDA recently granted a priority review designation to a supplemental biologics license application (sBLA) for the frontline immunotherapy combination of atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) for the treatment of patients with unresectable locally advanced or metastatic PD-L1–positive TNBC.
The sBLA is based on data from the phase III IMpassion130 trial, which found that the addition of atezolizumab to nab-paclitaxel reduced the risk of disease progression or death by 38% compared with nab-paclitaxel alone in this population.1
Another therapy that is under investigation and showing promise is the antibody-drug conjugate (ADC) sacituzumab govitecan (IMMU-132), which was granted a priority review designation by the FDA in July 2018 for patients with metastatic TNBC who have undergone at least 2 previous therapies.
In a phase II trial, sacituzumab govitecan was associated with a 34% objective response rate (ORR) in patients with heavily pretreated metastatic TNBC. In the single-arm trial, which enrolled 110 patients, the ORR was accompanied by a stable disease rate for ≥6 months in 11% of patients, leading an overall disease control rate of 45%. Median progression-free survival (PFS) was 5.5 months (95% CI, 4.8-6.6), and the median OS was 12.7 months (95% CI, 10.8-13.6).2
Another area of interest in this space is the use of PARP inhibitors, such as talazoparib (Talzenna) and olaparib (Lynparza), which were recently approved by the FDA for the treatment of patients with BRCA
In an interview during the 2018 OncLive®
State of the Science Summit™ on Breast Cancer, Brufsky, professor of Medicine, associate chief, Division of Hematology/Oncology, co-director, Comprehensive Breast Cancer Center, associate director, Clinical Investigation, University of Pittsburgh, highlighted novel treatment approaches being explored in the TNBC space.
OncLive: Could you provide an overview of your presentation on treatment approaches in TNBC?
: What I talked about today had to do mostly with the genomic assays for breast cancer—in particular, the 21-Gene recurrence score assay, which is Oncotype DX, and the 70-gene signature test, which is MammaPrint. I compared and contrasted 2 of the large randomized clinical trials that have been done—TAILORx for Oncotype DX and MINDACT for MammaPrint.
They both were interesting; it’s gratifying that they both measure the same thing; they identify a group of patients who do not require chemotherapy. In the case of TAILORx, it’s really for node-negative breast cancer, while with MammaPrint in the prospective trial, it was node-negative and node-positive disease. There will be node-positive data coming out from a trial called RxPONDER in the next few years as well.
What treatment approaches are being evaluated for patients with TNBC?
In TNBC, we are going to talk about the new data on checkpoint inhibitors, which are really exciting, especially for patients who are PD-L1 positive. Patients who are given these inhibitors have been shown to have a 2-year overall survival, which is double that of not having had the checkpoint inhibitor—that is really dramatic.
In my presentation, I spoke a bit about sacituzumab govitecan, which is an antibody-drug conjugate to the Trop-2 antigen; it also has a lot of exciting phase II data in the third-line setting and beyond in TNBC. A large randomized phase III trial is currently ongoing that is randomizing patients to receive either sacituzumab govitecan or the standard of care in TNBC, which is generally chemotherapy. This is exciting new research.
I also discussed the use of PI3K inhibitors in patients with TNBC. There’s a trial called PAKT, where women who had PI3K-, AKT-, or PTEN-mutated breast cancer were randomized to receive paclitaxel with or without the AKT inhibitor [AZD5363], and they had an overall survival benefit as well if they had a PI3K mutation.