Experts Debate Use of Platinum-Based Agents for Treatment of High-Risk TNBC

Matthew Ellis, MD, PhD, FRCP

Debu Tripathy, MD

Two leading breast cancer experts debated the proposition that platinum-based or other additional systemic agents should be used in difficult-to-treat cases of high-risk triple-negative breast cancer (TNBC), at the 33rd Annual Miami Breast Cancer Conference, held March 10–13 in Miami Beach, Florida.

Matthew Ellis, MD, PhD, FRCP, professor and director of the Lester and Sue Smith Breast Care Center, Baylor College of Medicine, in Houston, Texas, argued that the answer is “yes.” He squared off in a friendly debate against Debu Tripathy, MD, chair of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

Other systemic treatments should be used to supplement standard chemotherapy in TNBC, Dr. Ellis said. He cited pathologic complete response (pCR) findings from the CALGB 40603 (Alliance) trial, suggesting benefits with the addition of carboplatin to neoadjuvant once-weekly paclitaxel, doxorubicin, and cyclophosphamide in stage II/III TNBC.

“The real questions,” Dr. Ellis said, “are cyclophosphamide vs platin vs sequential therapy; how to deliver platin therapy, dose and schedule; and the unresolved role of platin radiotherapy in treatment-refractory TNBC.”

He also emphasized that it’s time to “incorporate immunology into our thinking” about TNBC drug efficacy.

But it is still too soon to recommend routine additional chemotherapy for these patients, countered Dr. Tripathy, who noted several potential “cons” to adding additional systemic treatments to standard adjuvant chemotherapy for patients with TNBC. For example, he said, delivered doses of standard therapies can be reduced when additional systemic treatments are given concurrently, and additional systemic therapies can mean more toxicity, including high-grade and long-lasting adverse events

“We have to be sure not to give patients what could be permanent side effects,” Dr. Tripathy said.

Both Dr. Ellis and Dr. Tripathy discussed the GeparSixto trial in their arguments for and against routine platinum for TNBC. Dr. Ellis pointed to improved pCR and disease-free survival (DFS) rates associated with neoadjuvant carboplatin in GeparSixto, while Dr. Tripathy cautioned that the higher DFS “may be due to the omission of an alkylator in the chemotherapy backbone” in that study.

The evidence base continues to grow and could soon shed new light on the question, Dr. Tripathy acknowledged. Recently reported phase III CREATE-X trial findings suggest that adding the oral fluoropyrimidine capecitabine to standard treatment can improve survival for patients with residual HER2-negative breast cancer. TNBC-specific subset analyses are ongoing.

“CREATE-X data are intriguing,” Dr. Tripathy said. But he cautioned that clinicians should await the final, published report on that study’s findings. “Fluoropyrimidines are metabolized differently in certain ethnicities-particularly Asians,” he noted.