Neoadjuvant breast cancer treatment as a sensitive setting for trastuzumab biosimilar development and extrapolation.

Aims: Identify sensitive end points and populations for similarity studies of trastuzumab and biosimilar monoclonal antibodies.

Methods: We performed meta-analyses of trastuzumab clinical trials data: overall response rate (ORR) and progression-free survival in metastatic breast cancer (MBC), and total pathologic complete response (tpCR) and event-free survival in the neoadjuvant setting. Fitted models predicted the maximum loss in long-term efficacy for different similarity trial designs.

Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma.

Background: The efficacy and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single-arm, open-label, multicenter trial.

Methods: Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.

Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure.

Purpose: This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib.

Materials And Methods: This open-label, multicentre, phase 2 trial of oral linifanib 0.25 mg/kg/day enrolled patients who had prior nephrectomy and adequate organ function.

Phase 2 trial of Linifanib (ABT-869) in patients with advanced non-small cell lung cancer.

Introduction: This study assessed activity and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, in patients with locally advanced or metastatic non-small cell lung cancer.

Methods: In this open-label trial (NCT00517790), patients who received one to two prior lines of systemic therapy were randomized to oral linifanib 0.10 mg/kg (low dose) or 0.

Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial.

Purpose: Because of promising efficacy signals in single-arm studies, a placebo-controlled, double-blind, randomized phase II trial was designed to assess the efficacy and safety of adding bevacizumab to first-line standard chemotherapy for treatment of extensive-stage small-cell lung cancer (SCLC).

Patients And Methods: Patients with SCLC were randomly assigned to receive bevacizumab or placebo, with cisplatin or carboplatin plus etoposide, for four cycles followed by single-agent bevacizumab or placebo until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS).

Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer.

Introduction: Bevacizumab (B) improves survival of patients with metastatic, nonsquamous non-small cell lung cancer. Based on encouraging results from preclinical studies combining B with sunitinib (S), a phase II, randomized, open-label study (Study Assessing the Blockade of both VEGF Receptor and ligand to enhance Efficacy in Lung) was initiated to assess clinical outcomes of adding S to paclitaxel (P)/carboplatin (C) + B (PCB) for first-line treatment of locally advanced, metastatic, or recurrent nonsquamous non-small cell lung cancer.

Methods: Study enrollment was to occur in three phases.

Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer.

Purpose: Bevacizumab (Bev) has clinical activity in advanced renal cell carcinoma (RCC), and, when combined with erlotinib (Erl), has shown encouraging objective response rate (ORR) and progression-free survival (PFS). We performed a phase II, randomized, double-blind, multicenter, placebo-controlled trial to assess whether Erl provides additional clinical benefit with regard to PFS and ORR when combined with Bev in first-line treatment of metastatic RCC.

Patients And Methods: One hundred four patients received intravenous Bev (10 mg/kg) every 2 weeks in combination with oral Erl (150 mg) or placebo daily.

Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab.

Background: Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed.

Combinatorial antiangiogenic gene therapy by nonviral gene transfer using the sleeping beauty transposon causes tumor regression and improves survival in mice bearing intracranial human glioblastoma.

Glioblastoma is a fatal brain tumor that becomes highly vascularized by secreting proangiogenic factors and depends on continued angiogenesis to increase in size. Consequently, a successful antiangiogenic therapy should provide long-term inhibition of tumor-induced angiogenesis, suggesting long-term gene transfer as a therapeutic strategy. In this study a soluble vascular endothelial growth factor receptor (sFlt-1) and an angiostatin-endostatin fusion gene (statin-AE) were codelivered to human glioblastoma xenografts by nonviral gene transfer using the Sleeping Beauty (SB) transposon.

Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab.

Background: Bevacizumab (Avastin; rhuMab VEGF), a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), significantly prolongs survival when added to intravenous 5-fluorouracil-based chemotherapy in first-line metastatic colorectal cancer (CRC) treatment. Because antiangiogenic agents might inhibit wound healing, we assessed postoperative wound healing complications in two randomized trials of 5 mg/kg bevacizumab in CRC treatment.

Methods: We assessed the wound healing complications in patients who: (1) underwent cancer surgery 28-60 days before study treatment and (2) underwent major surgery during study treatment.

The therapeutic potential of novel antiangiogenic therapies.

Promising new antiangiogenic strategies are emerging for the treatment of cancer. Numerous candidate drugs that target vascular endothelial growth factor, vascular endothelial growth factor receptors, integrins, matrix metalloproteinases and other blood vessel targets are being developed and tested in clinical trials. This review highlights the numerous drugs in clinical trials and expands on potential new approaches to inhibiting angiogenesis.

Mechanisms and future directions for angiogenesis-based cancer therapies.

Targeting angiogenesis represents a new strategy for the development of anticancer therapies. New targets derived from proliferating endothelial cells may be useful in developing anticancer drugs that prolong or stabilize the progression of tumors with minimal systemic toxicities. These drugs may also be used as novel imaging and radiommunotherapeutic agents in cancer therapy.