First-line bevacizumab-containing therapy for HER2-negative locally advanced/metastatic breast cancer: Real-world experience from >2000 patients treated in the multicentre AVANTI study

Abstract

Aim: The multicentre non-interventional AVANTI study assessed safety, effectiveness and patientreported outcomes with approved first-line bevacizumab-containing regimens for HER2-negative locally recurrent/metastatic breast cancer (LR/MBC) in German routine oncology practice. Methods: Eligible patients had HER2-negative LR/MBC, no bevacizumab contraindications and no prior chemotherapy for LR/MBC. Chemotherapy schedule, diagnostics and follow-up were at physicians' discretion. Data were collected for 1 year after starting bevacizumab, then every 6 months for 1.5 years (maximum follow-up: 2.5 years). Patients and physicians rated treatment satisfaction. Subgroup analyses were prespecified in clinically relevant populations, including triple-negative breast cancer (TNBC). Results: Between November 1, 2009 and April 30, 2016, 2065 eligible patients at 346 centres received bevacizumab with paclitaxel or capecitabine. Patients receiving bevacizumabecapecitabine were less likely to have de novo disease and more likely to have TNBC, age 60 years and prior anthracycline/ taxane and/or endocrine therapy. Median PFS was 12.6 (95% CI 11.9e13.2) months (12.8 with bevacizumabepaclitaxel, 10.5 with bevacizumabecapecitabine); median OS was 23.9 (95% CI 22.2e25.1) months. Outcomes were worse in patients with TNBC, prior anthracycline/taxane or prior endocrine therapy. Grade 3 adverse events occurred in 27% of patients. Treatment was discontinued for adverse events in 15%. Treatment satisfaction was rated as good or better by 304/394 responding patients (77%) at week 54 and in 1393/2065 patients (67%) by physicians overall. Conclusions: In routine clinical practice, effectiveness and safety of first-line bevacizumab-containing therapy for LR/MBC were consistent with experience from phase III trials. Patient and physician treatment satisfaction showed high concordance.

Front-Line Bevacizumab plus Chemotherapy with or without Maintenance Therapy for Metastatic Breast Cancer: An Observational Study by the Hellenic Oncology Research Group

“…There are also other real-world studies of BEV in combination to chemotherapy in mBC. The multicentric German study AVANTI included >2000 patients who received front-line therapy with BEV in combination to paclitaxel or capecitabine [ 18 ]. Median PFS was 12.6 and 10.5 months for the two chemotherapy regimens, respectively, and median OS was 31.4 months.…”

Factors affecting prognosis in patients treated with bevacizumab plus paclitaxel as first-line chemotherapy for HER2-negative metastatic breast cancer: an international pooled analysis of individual patient data from four prospective observational studies

“…Therefore, it was not possible to directly examine the efficacy of comparing bevacizumab plus paclitaxel and paclitaxel alone. Second, the category and duration of data collection in each observational study were different for each study because the primary endpoint in these four studies was different as follows; The ML21165 [ 10 ] and AVANTI (ML22452) [ 12 ] studies had no primary endpoint but prespecified endpoints such as safety and effectiveness (ORR, PFS and OS), and primary endpoint in the AVAREG (ML21647) [ 11 ] and the B-SHARE [ 13 ] studies were PFS and OS, respectively. Therefore, the median observation period at the time of this pooled analysis was relatively short.…”

“…This study is a collaborative pooled analysis using independent patient data from four prospective non-interventional studies to assess the effectiveness of bevacizumab in combination with paclitaxel as first-line chemotherapy for metastatic breast cancer. These four observational studies included ML21165 [ 10 ], ML21647 [ 11 ], ML22452 [ 12 ], and B-SHARE [ 13 ], (Supplementary Table 1). The main results of these four studies have already been published individually [ 10 – 13 ].…”

“…Recently, large-scale observational studies are becoming increasingly important as complementary tools for randomized control trials, several non-interventional studies have evaluated the effectiveness and safety of bevacizumab plus paclitaxel for HER2-negative advanced breast cancer patients in the real world [ 9 ]. We conducted this pooled analysis with individual patient data from four prospective observational studies, ML21165 [ 10 ], ML21647 [ 11 ], ML22452 [ 12 ] and B-SHARE [ 13 ], to more accurately estimate the effectiveness of bevacizumab plus paclitaxel and to evaluate effectiveness in selected subgroups such as triple-negative subtype. We also tried to identify prognostic factors in terms of survival in this pooled analysis.…”

Apatinib plus vinorelbine versus vinorelbine for metastatic triple-negative breast cancer who failed first/second-line treatment: the NAN trial

“…Anti-angiogenic drugs have been gradually attempted in the treatment of TNBC due to its higher expression of VEGF and VEGFR compared with other subtypes of breast cancer, despite the side effects of bleeding, hypertension, and thrombus [11][12][13] . Since 2009, several phase III trials have investigated antiangiogenesis molecular targeted therapies in metastatic TNBC [14][15][16] .…”