The Efficacy of Combining Antiangiogenic Agents with Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer Who Failed First-Line Chemotherapy: A Systematic Review and Meta-Analysis

Abstract

BackgroundThe clinical outcomes of patients with NSCLC who progressed after first-line treatments remain poor. The purpose of this study was to assess the advantage of antiangiogenic therapy plus standard treatment versus standard treatment alone for this population of patients.MethodsWe conducted a rigorous search using electronic databases for eligible studies reporting antiangiogenic therapy combined with standard second-line chemotherapy versus standard second-line treatment for patient who progressed after front-line treatment. Pooled risk ratio and 95% confidence intervals were calculated using proper statistical method. Predefined subgroup analyses were conducted to identify the potential proper patients.ResultsThirteen phase II/III RCTs which involved a total of 8358 participants were included. Overall, there was significant improvement in OS (HR 0.94, 95%CI: 0.89-0.99, p=0.03), PFS (HR 0.80, 95%CI: 0.76-0.84, p<0.00001), ORR (RR 1.75, 95%CI: 1.55-1.98, p<0.00001) and DCR (RR 1.23, 95%CI: 1.18-1.28, p<0.00001) in the group with antiangiogenic therapy plus standard treatment versus the group with standard treatment alone. Subgroup analysis showed that OS benefit was presented only in patients treated with docetaxel plus antiangiogenic agents (HR 0.92, 95%CI: 0.86-0.99, p=0.02) and patients with non-squamous NSCLC (HR for OS 0.92, 95%CI: 0.86-0.99, p=0.02).ConclusionsThis study revealed that the addition of antiangiogenic agents to the standard treatments could provide clinical benefit to NSCLC patients who failed their first-line therapy. Furthermore, proper selection of the combined standard cytotoxic agent, as well as the patient population by tumor histology, is warranted for future studies and clinical application of antiangiogenic therapy.

The Evaluation of Durative Transfusion of Endostar Combined with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

“…Therefore, anti-angiogenesis has represented a new approach for targeted cancer therapy [6]. Recent clinical studies have demonstrated patients with advanced SCLCs benefitting further from anti-angiogenic therapy, when combined with chemotherapeutic regimes [7, 8]. …”

Angiogenesis inhibitors for the treatment of small cell lung cancer (SCLC)

“…On the contrary, numerous studies suggested angiogenesis inhibitors were generally demonstrated to be effective to NSCLC. [41–44] Particularly, Gao et al [45] conducted a meta-analysis encompassing over 452 advanced NSCLC patients who previously received bevacizumab and found that angiogenesis inhibitors improved clinical benefits. Therefore, different subtypes of diseases should be considered when using angiogenesis inhibitors in lung cancer.…”

Historical Evolution of Second-Line Therapy in Non-Small Cell Lung Cancer

“…Angiogenesis acts as one of the essential alterations occurring in cells during malignant transformation (56), since the delivery of oxygen and nutrients, provided by blood vessels, is required for cell survival and proliferation. Different molecules, inhibiting the angiogenic regulators, have been tested in combination with second-line chemotherapy (pemetrexed and docetaxel) in patients with NSCLC, but with disappointing results (62). Only recently, two drugs, interfering with the angiogenic pathways, nintedaninb and ramucirumab, have received the regulatory approval in association with docetaxel in the second-line setting.…”