Commenting on the study from Tata Memorial Centre for The ASCO Post, Adam M. Brufsky, MD, Professor of Medicine, Associate Chief of the Division of Hematology/Oncology and Co-Director of the Comprehensive Breast Cancer Center at the University of Pittsburgh School of Medicine, noted that the addition of carboplatin to standard neoadjuvant chemotherapy for early-stage triple-negative breast cancer has been controversial.
Initial data from CALBG 406031 demonstrated improved rates of pathologic complete response with the addition of carboplatin to standard chemotherapy but did not demonstrate a statistically significant survival benefit. Adjuvant carboplatin also provided no progression-free survival benefit when compared to capecitabine in women with early-stage triple-negative breast cancer and residual disease after neoadjuvant therapy in the phase III ECOG-ACRIN E1131 study.2
Adam M. Brufsky, MD
On the other hand, data from GeparSixto3 (which used an uncommon neoadjuvant regimen) and BrighTNess4 (which studied the addition of a PARP inhibitor to neoadjuvant chemotherapy and did not meet its primary endpoint of pathologic complete response) did demonstrate increased disease-free survival and event-free survival, respectively, as secondary endpoints with the addition of carboplatin. Carboplatin is included in the KEYNOTE-5225 neoadjuvant regimen in combination with standard chemotherapy and pembrolizumab, which has rapidly become a standard of care for early-stage triple-negative breast cancer in the United States, he said.
Further Considerations
“The trial from Tata Memorial Centre appears to be well conducted, with appropriately powered endpoints, in a high-risk population (88% node-positive disease, 77% tumors larger than 5 cm). The demonstration of a pathologic complete response benefit is consistent with prior studies, and the trial also demonstrated an event-free and overall survival benefit in the subgroup of women under 50 or who were premenopausal. The authors of the trial were not able to explain the basis for this result, and there were no other interactions with any other subgroups such as family history, tumor size, or tumor grade,” he said.
“While we await final publication of these results, the Tata trial does suggest a survival benefit of carboplatin in young or premenopausal women with higher-risk triple-negative breast cancer. But carboplatin is not without toxicity, including additional neuropathy and neutropenia when added to standard neoadjuvant regimens. The Tata trial adds to the evidence suggesting a judicious use of carboplatin added to standard neoadjuvant therapy in particular high-risk subgroups,” Dr. Brufsky concluded.
DISCLOSURE: Dr. Brufsky reported financial relationships with AstraZeneca, Pfizer, Novartis, Lilly, Genentech/Roche, Seagen, Daiichi Sankyo, Merck, Agendia, Sanofi, and Puma Biotechnology.
REFERENCES
1. Shepherd JH, Ballman K, Polley MYC, et al: CALGB 40603 (Alliance): Long-term outcomes and genomic correlates of response and survival after neoadjuvant chemotherapy with or without carboplatin and bevacizumab in triple-negative breast cancer. J Clin Oncol 40:1323-1334, 2022.
2. Mayer IA, Zhao F, Arteaga CL, et al: Randomized phase III postoperative trial of platinum-based chemotherapy versus capecitabine in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: ECOG-ACRIN EA1131. J Clin Oncol 39:2539-2551, 2021.
3. Loibl S, Weber KE, Timms KM, et al: Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol 29:2341-2347, 2018.
4. Geyer CE, Sikov WM, Huober J, et al: Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase III trial. Ann Oncol 33:384-394, 2022.
5. Schmid P, Cortes J, Pusztai L, et al: Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382:810-821, 2022.
