Clin Cancer Res 2020 Nov 18
Randomized Phase II Trial of Anthracycline-free and Anthracycline-containing Neoadjuvant Carboplatin Chemotherapy Regimens in Stage I-III Triple-negative Breast Cancer (NeoSTOP).
Abstract
Purpose
Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response (pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in triple-negative breast cancer (TNBC). Aim of the NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens.
Patients and methods
Patients aged ≥18 years with stage I-III TNBC were randomized (1:1) to receive either paclitaxel (P) weekly × 12 plus carboplatin AUC6 every 21 days × 4 followed by doxorubicin/cyclophosphamide (AC) every 14 days × 4 (CbP → AC, arm A), or carboplatin AUC6 + docetaxel (D) every 21 days × 6 (CbD, arm B). Stromal tumor-infiltrating lymphocytes (sTIL) were assessed. Primary endpoint was pCR in breast and axilla. Other endpoints included residual cancer burden (RCB), toxicity, cost, and event-free (EFS) and overall survival (OS).
Results
One hundred patients were randomized; arm A (n = 48) or arm B (n = 52). pCR was 54% [95% confidence interval (CI), 40%-69%] in arm A and 54% (95% CI, 40%-68%) in arm B. RCB 0+I rate was 67% in both arms. Median sTIL density was numerically higher in those with pCR compared with those with residual disease (20% vs. 5%; P = 0.25). At median follow-up of 38 months, EFS and OS were similar in the two arms. Grade 3/4 adverse events were more common in arm A compared with arm B, with the most notable differences in neutropenia (60% vs. 8%; P < 0.001) and febrile neutropenia (19% vs. 0%; P < 0.001). There was one treatment-related death (arm A) due to acute leukemia. Mean treatment cost was lower for arm B compared with arm A (P = 0.02).
Conclusions
The two-drug CbD regimen yielded pCR, RCB 0+I, and survival rates similar to the four-drug regimen of CbP → AC, but with a more favorable toxicity profile and lower treatment-associated cost.
Related Questions
How do you interpret the EBCTCG meta-analysis analyzing the magnitude of benefit of anthracyclines in early stage ER+ breast cancer?
The appreciation of studies testing the specific benefit of adding or substituting anthracyclines as adjuvant therapy for early stage breast cancer requires a historical overview (so my apologies for a very long response….). Several of the earlier trials comparing non-anthracycline therapies (primar...
Would you consider using anthracycline for treating a Stage I triple negative breast cancer in a patient with a baseline mildly reduced LVEF 50-55%?
I'm going to assume this is the clinical stage, and the patient has not yet had surgery. In this arena, if the patient is a fit surgical candidate then there are those who might advocate for taking to surgery up front if they are otherwise healthy. In patients like this, you could have a look at the...
Would you consider omitting platinum from neoadjuvant chemotherapy in women > 50 years of age with localized triple negative breast cancer?
I would not use the results cited above from the >50 subgroup (which was just 30% of their study population) of the study from the Tata Memorial Centre to justify omission of carboplatin from the neoadjuvant regimen for TNBC in otherwise healthy patients over 50 with TNBC. There is compelling data f...