nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial

Abstract

BackgroundMetastatic triple-negative breast cancer (mTNBC) has a poor prognosis and aggressive clinical course. tnAcity evaluated the efficacy and safety of first-line nab-paclitaxel plus carboplatin (nab-P/C), nab-paclitaxel plus gemcitabine (nab-P/G), and gemcitabine plus carboplatin (G/C) in patients with mTNBC.Patients and methodsPatients with pathologically confirmed mTNBC and no prior chemotherapy for metastatic BC received (1 : 1 : 1) nab-P 125 mg/m2 plus C AUC 2, nab-P 125 mg/m2 plus G 1000 mg/m2, or G 1000 mg/m2 plus C AUC 2, all on days 1, 8 q3w. Phase II primary end point: investigator-assessed progression-free survival (PFS); secondary end points included overall response rate (ORR), overall survival (OS), percentage of patients initiating cycle 6 with doublet therapy, and safety.ResultsIn total, 191 patients were enrolled (nab-P/C, n = 64; nab-P/G, n = 61; G/C, n = 66). PFS was significantly longer with nab-P/C versus nab-P/G [median, 8.3 versus 5.5 months; hazard ratio (HR), 0.59 [95% CI, 0.38–0.92]; P = 0.02] or G/C (median, 8.3 versus 6.0 months; HR, 0.58 [95% CI, 0.37–0.90]; P = 0.02). OS was numerically longer with nab-P/C versus nab-P/G (median, 16.8 versus 12.1 months; HR, 0.73 [95% CI, 0.47–1.13]; P = 0.16) or G/C (median, 16.8 versus 12.6 months; HR, 0.80 [95% CI, 0.52–1.22]; P = 0.29). ORR was 73%, 39%, and 44%, respectively. In the nab-P/C, nab-P/G, and G/C groups, 64%, 56%, and 50% of patients initiated cycle 6 with a doublet. Grade ≥3 adverse events were mainly hematologic.ConclusionsFirst-line nab-P/C was active in mTNBC and resulted in a significantly longer PFS and improved risk/benefit profile versus nab-P/G or G/C.

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

“…The NCCN panel had included combination chemotherapy regimens as useful in certain circumstances. The combination regimen options include doxorubicin/ cyclophosphamide (AC) 154,155 ; epirubicin/cyclophosphamide (EC) 156 ; docetaxel and capecitabine 121 ; gemcitabine and paclitaxel (GT) 157 ; cyclophosphamide/methotrexate/ fluorouracil (CMF) 158 ; gemcitabine/carboplatin [159][160][161] ; carboplatin with paclitaxel or albumin-bound paclitaxel [162][163][164] ; and paclitaxel/bevacizumab. [165][166][167] For the doublet regimens that are included, randomized phase III trials have shown that the ORR with first-line AC treatment ranges from 47% to 54% and OS is around 20 months.…”

“…163,164 The randomized trial, tnAcity, evaluated the efficacy and safety of first-line albumin-bound paclitaxel plus carboplatin, albumin-bound paclitaxel plus gemcitabine, and gemcitabine plus carboplatin in patients with metastatic triple-negative breast cancer. 162 The results of this trial reported that median PFS was significantly longer with albumin-bound paclitaxel plus carboplatin versus albumin-bound paclitaxel/gemcitabine (8.3 vs 5.5 months; HR, 0.59; 95% CI, 0.38-0.92; P5.02) or gemcitabine/carboplatin (8.3 vs 6.0 months; HR, 0.58; 95% CI, 0.37-0.90; P5.02). The median OS was also longer with albumin-bound paclitaxel plus carboplatin versus albumin-bound paclitaxel/gemcitabine (16.8 vs 12.1 months; HR, 0.73; 95% CI, 0.47-1.13; P5.16) or gemcitabine/carboplatin (16.8 vs 12.6 months; HR, 0.80; 95% CI, 0.52-1.22; P5.29).…”

“…The ORRs were 73%, 39%, and 44%, respectively. 162 A series of trials have sought to define the role for bevacizumab in the treatment of metastatic breast cancer. The E2100 trial randomized 722 women with recurrent or metastatic breast cancer to first-line chemotherapy with paclitaxel with or without bevacizumab.…”

Hype or hope? The strange case of platinum salts’ renaissance in breast cancer

“…Determining the role of single-agent platinum salts has been challenging, while synergistic combinations have shown far more encouraging results in advanced TNBC. The phase 2 tnAcity trial suggested a solid rationale for the nab-paclitaxel/carboplatin doublet as first-line treatment in unselected TNBC patients, with a 73% response rate and improved PFS versus the nab-paclitaxel /gemcitabine (median PFS 8.3 vs 5.5 months; HR 0.59 [95% CI, 0.38-0.92]; p = 0.02) and gemcitabine/carboplatin combinations (median PFS 8.3 vs 6.0 months; HR 0.58 [95% CI, 0.37-0.90]; p = 0.02) [4].…”

The prospects for cisplatin and nab-paclitaxel combination therapy in patients with pre-treated triple-negative breast cancer. Description of the clinical case.

“…для группы терапии гемцитабин + карбоплатин (ОР-0,58, р = 0,02). Показатели общей выживаемости были также выше в группе наб-паклитаксела с карбоплатином, однако статистически значимой разницы не достигнуто [24].…”