In a phase II trial (INFORM; Translational Breast Cancer Research Consortium [TBCRC] 031) reported in the Journal of Clinical Oncology, Nadine Tung, MD, and colleagues found that neoadjuvant cisplatin did not improve pathologic complete response rate or residual cancer burden vs doxorubicin/cyclophosphamide in patients with early HER2-negative breast cancer who are BRCA-mutation carriers.
Nadine Tung, MD
In the multicenter trial, 117 evaluable patients with stage I to III disease were randomly assigned between January 2012 and January 2019 to receive neoadjuvant cisplatin at 75 mg/m² every 3 weeks for four doses (n = 60) or doxorubicin at 60 mg/m² and cyclophosphamide at 600 mg/m² every 2 to 3 weeks for four doses (n = 57) followed by surgery. Overall, 69% of patients had a BRCA1 mutation, 30% had a BRCA2 mutation, and 2% had both mutations.
The primary goal of the study was to determine if pathologic complete response was ≥ 20% higher with cisplatin vs doxorubicin/cyclophosphamide. Secondary objectives included comparison of residual cancer burden scores of 0 or 1 combined. The study was closed in February 2019 because of slow accrual.
Among all patients, a pathologic complete response was achieved in 18% of the cisplatin group vs 26% of the doxorubicin/cyclophosphamide group (risk ratio [RR] = 0.70, 90% confidence interval [CI] = 0.39–1.2). Among 82 patients with triple-negative breast cancer, a pathologic complete response was achieved in 23% vs 29%. Among 35 with estrogen receptor (ER)- or progesterone receptor (PR)-positive disease, pathologic complete response rates were 6% vs 21%.
Among all patients, a residual cancer burden of 0 or 1 was found in 33% of the cisplatin group vs 46% of the doxorubicin/cyclophosphamide group (RR = 0.73, 90% CI = 0.50–1.1). Residual cancer burden of 0 or 1 was found in 36% vs 47% of patients with triple-negative disease and 25% vs 42% of those with ER- or PR-positive disease.
According to the investigators, both regimens were generally well tolerated and presented no unexpected toxicities. The most common grade 3 or 4 toxicity was decreased neutrophils in both groups (7% vs 9%). There were 11 nonhematologic grade ≥ 3 toxicities in the cisplatin group vs 4 in the doxorubicin/cyclophosphamide group.
The investigators concluded: “Pathologic complete response or residual cancer burden [of] 0/1 is not significantly higher with [cisplatin] than with [doxorubicin/cyclophosphamide] in BRCA carriers with stage I–III HER2-negative breast cancer for both [triple-negative breast cancer] and ER-[positive]/HER2-negative disease.”
Dr. Tung, of Beth Israel Deaconess Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Breast Cancer Research Foundation, Susan G. Komen, and Myriad Genetics. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.