Pilot phase II study of metronomic chemotherapy in combination with bevacizumab in patients with advanced non-squamous non-small cell lung cancer

Abstract

Introduction The goal of this study was to explore the efficacy and tolerability of metronomic chemotherapy, a novel anti-angiogenic treatment strategy, in combination with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC) Methods Subjects with newly diagnosed stage IV NSCLC were treated with 4-week cycles of paclitaxel 80 mg/m2 and gemcitabine 300 mg/m2 weekly for three weeks, plus bevacizumab 10 mg/kg every two weeks. Radiologic assessments were performed every 8 weeks. The primary endpoint was progression free survival (PFS). An exploratory objective was to correlate plasma levels of angiogenic biomarkers with treatment response. Results Thirty-nine subjects were included in the intent to treat (ITT) analysis. The objective response rate (ORR) was 56%, the median PFS was 8.5 months, and median overall survival (OS) was 25.5 months. The PFS rate at 6, 12, and 24 months was 61%, 21%, and 11% respectively. The OS rate at 12 and 24 months was 74% and 53% respectively. Treatment was well tolerated, without significant myelosuppressive, gastrointestinal, or neurologic events. Subjects with less than median baseline values of angiopoietin-2 and IL-8 experienced significantly longer PFS. Longer OS was associated with subjects with less than the median baseline values for PLGF and angiopoietin-2. There were statistically significant differences in median values of several biomarkers between cycles 1 and 3 in subjects with objective responses. Conclusions The combination of paclitaxel and gemcitabine, delivered in a metronomic schedule, in combination with bevacizumab, appears to be an effective and tolerable treatment strategy in patients with advanced NSCLC.

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

“…A metronomic regimen of paclitaxel and gemcitabine was tested with a combination of bevacizumab with additional markers of vascularization. In 39 advanced NSCLC patients, ORR was 56%, and median PFS rates at 6 and 12 months were 61% and 21%, respectively, with a median OS of 25.5 months [192]. As radiotherapy is a conventional option in elderly patients ineligible for cytotoxic therapy, a study evaluated the addition of metronomic regimens to radiotherapy; no significant clinical efficacy was observed [193].…”

Bevacizumab Plays a double-edged role in Neoadjuvant Therapy for Non-metastatic Breast Cancer: A Systemic Review and Meta-Analysis

“…A Pilot Phase II Study combining metronomic chemotherapy and Bev of 10mg/kg q14days have been demonstrated to be effective and tolerable strategy for advanced non-squamous Non-Small Cell Lung Cancer. [61] Lately, a RCT study from China (ClinicalTrials.gov Identifier: NCT01112826.) revealed that 1 year of low-dose capecitabine maintenance therapy helped to improve TNBC patients' DFS.…”

Phase 1b trial of nintedanib in combination with bevacizumab in patients with advanced solid tumors

“…We therefore chose blood based biomarker analysis where serial samples was collected at pre-specified intervals as it could assess the changes in molecular phenotype and also possible inter and intra-tumoral heterogeneity. Previous work demonstrated prognostic significance of variations in plasma angiogenic biomarkers relative to median values 17,23, 24 . Better DCR was correlated with lower baseline PIGF levels, as well as increased level from baseline.…”