The results come from a phase 2 trial that involved 100 women. The study was published online in February in Clinical Cancer Research.
The doublet provides a safe, effective alternative for patients who are not candidates for treatment with anthracyclines and should be explored further for neoadjuvant deescalation, according to investigators led by Priyanka Sharma, MD, TNBC specialist and professor at the University of Kansas Medical Center, Westwood.
The trial wasn’t powered to demonstrate noninferiority, so it “probably does not provide enough evidence to state that [taxane/platinum] should replace other regimens,” Dr. Sharma said in an interview.
A proper noninferiority trial would require more than 2,500 participants, she said, adding that such a trial is unlikely, because companies are focused on immunotherapies for neoadjuvant TNBC.
“Our study does, however, provide a very effective alternative for patients and providers who want to use or prefer an anthracycline-sparing neoadjuvant chemotherapy regimen. We are very encouraged” by the findings, Dr. Sharma said.
This is “a provocative study that should make us pause and reevaluate our current approach. Further study of this approach in early-stage TNBC is warranted,” Melinda L. Telli, MD, associate professor of medicine and director of the breast cancer program at Stanford (Calif.) University, said when asked for comment.
Avoiding the risks associated with anthracycline “is great. I would be particularly enthusiastic using this regimen in patients with known increased risk of cardiac toxicity,” said Amy Tiersten, MD, a breast cancer specialist and professor at Mount Sinai Hospital, New York.
Anthracycline-based regimens are the standard of care for neoadjuvant TNBC. They typically include a taxane with or without carboplatin plus an anthracycline/cyclophosphamide combination. The regimen is highly active, but there is a small but serious risk for cardiomyopathy and leukemia with anthracycline/cyclophosphamide. In the current trial, one woman in the anthracycline arm died of secondary acute myeloid leukemia.
Given its tolerability and effectiveness, a taxane/carboplatin doublet might serve as a good backbone for the addition of novel immunotherapies in trials. Dr. Sharma is the principal investigator in one such trial, a phase 2 trial of carboplatin/docetaxel plus pembrolizumab for stage I–III TNBC.
Study details
The Neoadjuvant Study of Two Platinum Regimens in Stage I–III Triple Negative Breast Cancer (NeoSTOP) involved 100 women with stage I–III TNBC.
In the experimental arm, 52 women received carboplatin AUC 6 plus docetaxel 75 mg/m2 every 21 days for six cycles.
In the standard-of-care anthracycline arm, 48 women received carboplatin AUC 6 every 21 days for four cycles plus paclitaxel 80 mg/m2 weekly for 12 weeks, followed by doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 2 weeks for four cycles.
Docetaxel and paclitaxel in the two regimens are interchangeable because they have shown equal efficacy in adjuvant trials, Dr. Sharma said.
At surgery, 54% of women in both arms had a breast/axilla pathologic complete response – the primary endpoint – and 67% in both arms had a residual cancer burden of 0-1. Event-free and overall survival (about 55% at 3 years for both) were similar with the two regimens.
Grade 3/4 adverse events were more common in the anthracycline arm. They included neutropenia, which occurred in 60% of women in the anthracycline arm, vs. 8% with the doublet; and febrile neutropenia, which occurred in 19% with anthracycline, vs. none with the doublet.
The toxicity profile of the anthracycline regimen was comparable to those in previous reports.
Ninety-two percent of the docetaxel/carboplatin group completed all six cycles; 72% of women in the anthracycline arm completed 10 or more doses of paclitaxel, and 85% completed all 4 carboplatin doses.
Mean costs of treatment, patient transportation, and lost productivity were $36,720 in the anthracycline arm, vs. $33,148 with the doublet.
The two arms were well balanced with respect to patient characteristics. The median age was 51 years, 30% of patients had axillary lymph node–positive disease, and 16% had ER/PgR expression of 1% to 10%. Of the study population, 17% carried deleterious BRCA1/2 mutations. Women were enrolled from July 2015 to May 2018. Median follow-up was 38 months.
Of the study population, 17% had stage I disease, so NeoSTOP included a lower-risk population than some neoadjuvant trials. However, there was no significant change in pathologic complete response rates in the two arms after exclusion of women with stage I disease (doublet, 50%; anthracycline, 54%).
The study was funded by the University of Kansas Cancer Center, the Breast Cancer Research Foundation, and the National Institute of General Medical Sciences. The investigators disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.