Phase III study on efficacy of taxanes plus bevacizumab with or without capecitabine as first-line chemotherapy in metastatic breast cancer

Abstract

Taxanes (T) plus bevacizumab (B) and taxanes plus capecitabine (X) showed better progression-free survival (PFS) compared to taxanes alone. Since life-threatening or highly symptomatic situations require polychemotherapy in metastatic breast cancer (MBC), combination of taxanes, capecitabine plus bevacizumab appears reasonable. TABEA (NCT01200212), a prospectively randomized, open-label, phase III trial compares taxanes (paclitaxel 80 mg/m(2) i.v. d1,8,15 q22 or docetaxel 75 mg/m(2) i.v. d1 q22) plus bevacizumab (15 mg/kg i.v. d1 q22) with (TBX) or without capecitabine (TB, 1800 mg/m(2) daily d1-14 q22) as first-line therapy in MBC. Histologically confirmed HER2-negative, locally advanced or MBC patients with a chemotherapy indication and measurable or non-measurable target lesions (RECIST criteria) were included. Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (complete response, partial response, stable disease ≥24 weeks), 3-year overall survival, PFS in patients ≥65 years, toxicity, and compliance. We assumed 10 and 13.3 months PFS for TB and TBX, respectively (HR = 0.75), requiring 432 patients and 386 events. Preplanned interim futility and safety analyses after 100 events in 202 patients showed no efficacy benefit and higher toxicity for TBX. Recruitment and therapy were stopped following advice from the IDMC. Final analysis revealed a HR 1.13 [95 %CI 0.806-1.59], P = 0.474, for PFS. Overall grade 3-4 adverse event (77.3 vs. 62.1 %, P = 0.014) and serious adverse event (40.0 vs. 30.2 %, P = 0.127) rates were higher for TBX after 26.1 months median follow-up, with six deaths for TBX versus 1 for TB. Adding capecitabine to TB cannot be recommended as first-line therapy in MBC.

Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

“…In contrast, a meta-analysis of phase III trials found that combination chemotherapy regiments showed a better time to progression, but not overall survival, in metastatic BC patients [17]. Similarly, it was noticed that a combined schedule, for instance, taxanes (paclitaxel or docetaxel) plus bevacizumab, displayed a higher progression-free survival versus taxanes alone (10 vs. 13.3 months; p = 0.474) as first line chemotherapy in metastatic BC [18]. Nonetheless, in spite of several schedule options, patients frequently relapse after chemotherapy treatment as a result of the acquired resistance of the tumor cells or by signals drivens by the microenvironment in order to enhance the cancer stem cells which are resistant to different treatments [19].…”

Optimizing the treatment of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer: an updated meta-analysis of published randomized trials

“…Based on the search strategy, 7 eligible trials with a total of 3,984 patients were identified and included in this meta-analysis (Figure S1). 12,13,16–20 The details of these included studies are summarized in Table 1. Three of these studies were used to evaluate the efficacy of adding bevacizumab to chemotherapy, including 1,558 women who received bevacizumab combined with chemo-therapy and 896 women who were administered chemotherapy alone 12,13,17.…”

“…Three of these studies were used to evaluate the efficacy of adding bevacizumab to chemotherapy, including 1,558 women who received bevacizumab combined with chemo-therapy and 896 women who were administered chemotherapy alone 12,13,17. The other 4 trials were obtained to assess the optimal chemotherapy partner of bevacizumab 16,18–20. All of them were published as full articles and described as Phase III randomized controlled trials.…”

“…All of them were published as full articles and described as Phase III randomized controlled trials. The former 3 trials were double blinded,12,13,17 and the latter 4 studies were open label 16,18–20. Of note, the E2100 trial was considered ineligible for this meta-analysis despite its inclusion in the previous reports on this topic 21,22.…”

Molecular-Targeted Therapy For Malignant Mesothelioma

“…The efficacy of antiangiogenic agents in several types of cancer was also examined, and some were used at a clinical level. [13][14][15] Most recently, inhibition of immunological checkpoints such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) molecules produced long-lasting antitumor effects, and consequently, we realized that immunotherapy can play a central role in cancer treatment. 16 Similarly, an investigation into MPM at the molecular level led to several clinical trials with molecular-targeted agents.…”