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
Study Details
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.
Key Findings
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%.
KEY POINTS
- Among all patients, pathologic complete response was achieved in 18% of the cisplatin group vs 26% of the doxorubicin/cyclophosphamide group.
- Among all patients, residual cancer burden of 0/1 was found in 33% of the cisplatin group vs 46% of the doxorubicin/cyclophosphamide group.
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.
