Adam M. Brufsky, MD, PhD
Compared with estrogen receptor (ER)–positive and HER2-positive breast cancer, triple-negative breast cancer (TNBC) is typically more aggressive and carries a higher mortality rate. Several ongoing clinical trials are attempting to gain ground. In February, the antibody–drug conjugate sacituzumab govitecan (IMMU-132) received a breakthrough therapy designation based on phase II trial data showing a response rate of 31% in heavily pretreated patients with metastatic TNBC. However, treatment advances are lagging behind those seen in other breast cancer phenotypes.
Panelists taking part in a recent OncLive
Peer Exchange® program provided context to the emerging evidence in TNBC, highlighting some of the key clinical trial data presented at the 2015 San Antonio Breast Cancer Symposium (SABCS). Moderated by Adam M. Brufsky, MD, PhD, the panel shed light on the impact this recent evidence may have on clinical practice.
One area open for debate is whether platinum agents should be added on to standard chemotherapy in the neoadjuvant setting of TNBC. Data from two clinical trials presented at 2015 SABCS pulled back one layer of the onion regarding neoadjuvant use of carboplatin, but are the data robust enough to change what clinicians do in clinical practice?
The phase II GeparSixto study evaluated the addition of carboplatin to weekly paclitaxel plus non-pegylated liposomal doxorubicin (Myocet) for 18 weeks in TNBC and HER2-positive breast cancer. Patients with TNBC (n = 315) received concurrent bevacizumab, while those with HER2-positive disease received trastuzumab and lapatinib. The carboplatin dose was reduced from area under the curve (AUC) 2.0 to AUC 1.5 to improve tolerability.1
In patients with TNBC, carboplatin improved the pathologic complete response (pCR) from 36.9% to 53.2% (P
= .005). However, the pCR improvement was not statistically significant in the HER2-positive subgroup (36.8% vs 32.8%, respectively; P
The study also showed a disease-free survival (DFS) benefit with carboplatin in the TNBC group after a median of 35 months (85.8% vs 76.1%; P
In addition, in patients with BRCA
wild-type tumors, the odds ratio (OR) for pCR was 2.09 in favor of carboplatin treatment compared with controls (50.8% vs 33.1%; P
= .005). In the BRCA
-mutant patients, the OR for pCR was 1.6 in favor of carboplatin, but the difference was not statistically significant (61.5% vs 50.0%; P
Hope S. Rugo, MD
Prior to this study, it was thought that platinum compounds are not active in patients without germline BRCA
mutations, said Christy A. Russell, MD. She noted that before she saw the GeparSixto findings, she was not in favor of adding carboplatin to neoadjuvant chemotherapy. She commented that the advantage in BRCA
wild-type TNBC was seen “not only in pathologic complete response rate, but also what appears to be translating into disease-free survival by the addition of carboplatin. And it has now made me think about it a little more. I have not yet added it.”
Joyce A. O’Shaughnessy, MD, pointed out that updated data from the CALGB 40603 trial, also presented at the conference, showed higher pCR, but no DFS improvement when carboplatin is added to once weekly paclitaxel in patients with stage II/III TNBC.2
The standard chemotherapy regimen for this trial was weekly paclitaxel 80 mg/m2 for 12 courses plus dose-dense doxorubicin and cyclophosphamide. Patients were randomized in a 2 x 2 schema to receive the standard regimen alone or the standard plus one of these regimens: bevacizumab every 2 weeks for 9 cycles; carboplatin AUC 6 every 3 weeks for 4 cycles; or the combination of bevacizumab and carboplatin.2
The pCR rates in the breast, the primary endpoint of the initial study, were 60% for patients receiving carboplatin and 46% in patients who did not receive carboplatin, an increase of 76% (P
In follow-up data presented at 2015 SABCS, Sikov and colleagues reported that patients who achieved a pCR on any arm of the study achieved far superior event-free survival and overall survival outcomes compared with those who did not have a pCR.2