Neoadjuvant, Anthracycline-Free Chemotherapy with Carboplatin and Docetaxel in Triple-Negative, Early-Stage Breast Cancer: A Multicentric Analysis of Feasibility and Rates of Pathologic Complete Response

Abstract

Background: Triple-negative breast cancer (TNBC) attracts a disproportionate share of intensive research because of its poor prognosis. Standard anthracycline- and taxane-based regimens still yield an unsatisfactorily low rate of pathologic complete response (pCR). The pCR rate is a recognized surrogate marker for good long-term survival. Methods: A multicentric, retrospective study was conducted including all patients not willing to undergo or not suitable for an anthracycline-based regimen. Six cycles of docetaxel 75 mg/m² and carboplatin AUC 6 q3w were administered. The primary endpoint was pCR (ypT0/ypTis + ypN0) and near-pCR (≤5 mm residual disease). The secondary endpoint was feasibility (CTCAE version 4.03 criteria) and adherence to treatment. Results: Six cycles of carboplatin AUC 6 and docetaxel 75 mg/m² resulted in a high pCR rate of 50% and a combined pCR/near-pCR rate of 70%. Grade 3 and 4 toxicities were rare events and 28 of 30 (93%) patients completed all 6 cycles. No toxicity-related treatment discontinuation and no febrile neutropenia were registered. Conclusion: This chemotherapy regimen provides a highly effective and feasible strategy for patients not willing to receive or not suitable for an anthracycline-based treatment (cardiac ejection fraction <65% or age >65 years). Combinations of platinum compounds with taxanes and anthracyclines may be also desirable in TNBC.

Biology and Management of Patients With Triple-Negative Breast Cancer

“…Three randomized studies have demonstrated that the addition of neoadjuvant carboplatin to anthracycline/taxane-based chemotherapy improves pCR in patients with stage I-III TNBC (pCR improved from 41% to 54% with addition of carboplatin) [70][71][72]. Other investigators studying anthracycline-free platinum regimens have reported encouraging pCR rates ranging from 36% to 65% [68,[73][74][75][76].…”

Oncolytic virotherapy for treatment of breast cancer, including triple-negative breast cancer

“…Since our in vivo study was conducted in immunodeficient mice, which lack T-cells, the results suggest that low-dose CP had a significant impact on inhibition of tumor growth via a mechanism other than depletion of regulatory T-cells. 7,19 Overall, it can be concluded that Ad5/3-D24-GMCSF displays effective antitumour activity in a TNBC xenograft model with concomitant 3 Yes PET-CT: PMD (-22% in injected lesions C two new mets) 4 CEA: CR (-70%) 239…”

“…3 TNBC is typically treated with a combination of therapies such as surgery, radiation therapy, and chemotherapy. 4 The relatively aggressive clinical course, poor prognosis, and limited treatment choices highlight the need for research in this patient group. A classic but little explored concept in the treatment of cancer is the use of low-dose metronomic chemotherapy regimens, which aims to ablate the dividing endothelial cells in tumors (preventing angiogenesis) 5 and to alter the immunological tumor microenvironment, thus hindering tumor growth.…”

Therapy With Carboplatin and Anti-PD-1 Antibodies Before Surgery Demonstrates Sustainable Anti-Tumor Effects for Secondary Cancers in Mice With Triple-Negative Breast Cancer

“…As deficiency in DNA damage repair is a signature of TNBC (2,5), interstrand crosslinking agents that bind DNA like carboplatin (CBDCA) have been tested in clinical trials, where CBDCA shows advantages in improving the rate of pathological complete response (6). Similar benefits of CBDCA have been observed in non-randomized studies (7)(8)(9)(10). These clinical data highlight the potential clinical application of CBDCA in TNBC patients.…”