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.

Neoadjuvant approach as a platform for treatment personalization: focus on HER2-positive and triple-negative breast cancer

“…Subgroup analysis revealed a larger magnitude of benefit in patients with earlier clinical stage [86]. In the NeoSTOP study, pCR rates were found to be similar between the anthracyclinecontaining versus anthracycline-free arm, with also similar EFS and OS [87]. As expected, the anthracycline-free arm was associated with higher rates of treatment completions and lower health-related costs.…”

Neoadjuvant docetaxel plus carboplatin vs epirubicin plus cyclophosphamide followed by docetaxel in triple‐negative, early‐stage breast cancer (NeoCART): Results from a multicenter, randomized controlled, open‐label phase II trial

“…As a result, National Comprehensive Cancer Network (NCCN) guidelines have added weekly paclitaxel plus carboplatin or docetaxel plus carboplatin regimens for select patients with TNBC in the preoperative setting 18 . Recently published NeoSTOP study was con rmed that the pCR and RCB 0 + 1 rates of carboplatin plus docetaxel (CbD) were similar to carboplatin plus paclitaxel followed by doxorubicin plus cyclophosphamide 19 .…”

Neoadjuvant Chemotherapy of Triple-Negative Breast Cancer: Evaluation of Early Clinical Response, Pathological Complete Response Rates, and Addition of Platinum Salts Benefit Based on Real-World Evidence

“…Another published meta-analysis evaluating the role of platinum salts in BRCA mutated TNBC patients showed that adding platinum increases pCR rate without statistical significance [ 66 ]. Recently published prospective trial NeoSTOP evaluated carboplatin-containing NACT presented a higher pCR rate in BRCA mutated TNBC patients on the borderline of significance, but this study included only platinum-based regimens [ 67 ].…”

“…In the GeparSixto trial, the addition of carboplatin was associated with a higher rate of hematological and non-hematological toxicity, and the dose of carboplatin was reduced from AUC 2.0 to AUC 1.5 [ 29 ]. On the other hand, a more favorable toxicity profile was observed for the AC-free carboplatin regimen in the NeoSTOP trial [ 67 ]. According to our study results, toxicity was more common in patients with platinum NACT but especially lower grades.…”