Antiangiogenic Agents Combined with Chemotherapy in the First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: Overall and Histology Subgroup-Specific Meta-Analysis

Abstract

Aim: This study investigated the overall and histology subtype-specific results of antiangiogenic agents combined with chemotherapy versus chemotherapy alone for the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Methods: Literature retrieval, trial selection, data collection, and statistical analysis were performed according to the Cochrane Handbook. The outcome measures were tumor response rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Results: 13 randomized controlled trials comprising 5,451 patients were included. The meta-analysis showed a higher response rate (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.53-0.74) and a significantly prolonged PFS (hazard ratio (HR) 0.75, 95% CI 0.66-0.85) and OS (HR 0.92, 95% CI 0.86-0.98) in the groups combining antiangiogenic agents with chemotherapy versus the chemotherapy alone groups. In the histology subgroup analysis, treatment with antiangiogenic agents plus chemotherapy significantly improved the RR, PFS, and OS as compared with the chemotherapy groups in patients with nonsquamous NSCLC, but not in those with squamous NSCLC. The risk of grade 3/4 thrombocytopenia, hypertension, bleeding, proteinuria, rash, diarrhea, fatigue, headache, anorexia, and febrile neutropenia was significantly increased in the antiangiogenic agent combination groups as compared with the chemotherapy groups. Conclusion: The use of antiangiogenic agents in addition to chemotherapy is a valid option for the first-line treatment of advanced NSCLC. The benefit is restricted to patients with nonsquamous-cell tumors.

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour‐bearing dogs: A phase I dose finding study

“…Proposed mechanisms include: (1) reducing the primary tumour's vascularity and vascular permeability, thereby reducing metastatic shedding, (2) contributing to a micromolecularly unfavourable metastatic niche, (3) primary and secondary tumour hypoxia and (4) somewhat counter‐intuitively improving tumour vascular patency, thereby enhancing delivery of the cytotoxic chemotherapeutic to the tumour . In the human field, combination therapy with an anti‐angiogenic agent and conventional MTD chemotherapy has demonstrated benefit in the treatment of non‐small cell lung cancer, colorectal cancer, breast cancer, urogenital carcinomas, malignant melanoma and several advanced stage diseases . However, benefit is not replicated in all clinical scenarios, and further elucidation of the ideal agents and combinations, tumour targets, optimal doses and scheduling regimens is required …”