Carboplatin-Cyclophosphamide or Paclitaxel without or with Bevacizumab as First-Line Treatment for Metastatic Triple-Negative Breast Cancer (BOOG 2013-01)

Abstract

<b><i>Background:</i></b> The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival (OS) benefit has been reported. Also, its combination with carboplatin-cyclophosphamide (CC) has never been investigated. <b><i>Methods:</i></b> The Triple-B study is a multicenter, randomized phase IIb trial that aims to prospectively validate predictive biomarkers, including baseline plasma vascular endothelial growth factor receptor-2 (pVEGFR-2), for bevacizumab benefit. mTNBC patients were randomized between CC and paclitaxel (P) without or with bevacizumab (CC ± B or P ± B). Here we report on a preplanned safety and preliminary efficacy analysis after the first 12 patients had been treated with CC+B and on the predictive value of pVEGFR-2. <b><i>Results:</i></b> In 58 patients, the median follow-up was 22.1 months. Toxicity was manageable and consistent with what was known for each agent separately. There was a trend toward a prolonged PFS with bevacizumab compared to chemotherapy only (7.0 vs. 5.2 months; adjusted HR = 0.60; 95% CI 0.33–1.08; <i>p</i> = 0.09), but there was no effect on OS. In this small study, pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Both the intention-to-treat analysis and the per-protocol analysis did not yield a significant treatment-by-biomarker test for interaction (<i>p</i><sub>interaction</sub> = 0.69). <b><i>Conclusions:</i></b>CC and CC+B are safe first-line regimens for mTNBC and the side effects are consistent with those known for each individual agent. pVEGFR-2 concentration did not predict a bevacizumab PFS benefit.

Efficacy and safety of taxanes combined with chemotherapy drugs in advanced triple negative breast cancer: A meta-analysis of 26 randomized controlled trials

“…After further identification, 163 studies were excluded due to erroneous control agents and no available data or duplicates. Finally, 26 full-text RCTs were included in this meta-analysis ( 13 – 16 , 40 – 61 ).…”

“…Among these 26 RCTs, 12 were designed as double-blind or placebo-controlled ( 13 , 42 – 44 , 46 , 50 , 51 , 53 , 55 – 57 , 60 ), 5 were designed as open-label or multicenter ( 14 , 16 , 40 , 52 , 61 ), and 9 were not described further in detail ( 15 , 41 , 45 , 47 – 49 , 54 , 58 , 59 ). The intervention arms in all trials were taxanes (nab-paclitaxel, 100 mg/m 2 ; paclitaxel, 80–175 mg/m 2 ; docetaxel, 75 mg/m 2 ) plus other chemotherapy drugs (atezolizumab, 7 trials; carboplatin, 3 trials; bevacizumab, 3 trials; gemcitabine, 2 trials; cisplatinum, 2 trials; oxaliplatin, 2 trials; ipatasertib, 2 trials; capecitabine, 1 trial; tigatuzumab, 1 trial; capivasertib, 1 trial; reparixin, 1 trial; cobimetinib, 1 trial), while the control arms were taxanes (17 trials) or other chemotherapy drugs (9 trials).…”

“…Taken together, our results indicated that taxanes-based combination therapies had a significant beneficial effect on prolonging PFS and OS index of advanced TNBC patients compared with taxanes monotherapy. In clinics, taxanes plus other chemotherapy drugs (i.e., platinum, tabines, bevacizumab, and atezolizumab) was broadly applied in the treatment of advanced TNBC ( 15 , 16 , 61 ). Our results of meta-analysis found that taxanes plus bevacizumab could evidently improve ORR index and decrease PD index in patients compared to bevacizumab plus other drugs ( p <0.05), but taxanes plus tabines or platinum revealed no statistical significance in therapeutic benefits compared to tabines or platinum plus other drugs ( p >0.05).…”