Addition of Bevacizumab to Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

IntroductionRecently, studies have demonstrated that the addition of bevacizumab to chemotherapy could be associated with better outcomes in patients with advanced non-small cell lung cancer (NSCLC). However, the benefit seems to be dependent on the drugs used in the chemotherapy regimens. This systematic review evaluated the strength of data on efficacy of the addition of bevacizumab to chemotherapy in advanced NSCLC.MethodsPubMed, EMBASE, and Cochrane databases were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated chemotherapy with or without bevacizumab in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), response rate (RR), toxicities and treatment related mortality. Hazard ratios (HR) and odds ratios (OR) were used for the meta-analysis and were expressed with 95% confidence intervals (CI).ResultsWe included results reported from five RCTs, with a total of 2,252 patients included in the primary analysis, all of them using platinum-based chemotherapy regimens. Compared to chemotherapy alone, the addition of bevacizumab to chemotherapy resulted in a significant longer OS (HR 0.89; 95% CI 0.79 to 0.99; p = 0.04), longer PFS (HR 0.73; 95% CI 0.66 to 0.82; p<0.00001) and higher response rates (OR 2.34; 95% CI 1.89 to 2.89; p<0.00001). We found no heterogeneity between trials, in all comparisons. There was a slight increase in toxicities in bevacizumab group, as well as an increased rate of treatment-related mortality.ConclusionsThe addition of bevacizumab to chemotherapy in patients with advanced NSCLC prolongs OS, PFS and RR. Considering the toxicities added, and the small absolute benefits found, bevacizumab plus platinum-based chemotherapy can be considered an option in selected patients with advanced NSCLC. However, risks and benefits should be discussed with patients before decision making.

Final Results of a Phase II Study of Bevacizumab, Cisplatin and Pemetrexed as First-Line Therapy for Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

“…These positive results of the addition of bevacizumab to a platinum doublet were corfirmed by the study or Crinò and colleagues [17]. This is a phase IV trial in which 2.012 stage III-B and IV untreated non-squamous NSCLC patients were treated with bevacizumab plus standard chemotherapy up to 6 cycles and, in case of no progressive disease, a maintenance period with bevacizumab monotherapy.…”

Phase II study of carboplatin, docetaxel and bevacizumab for chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer

“…With regard to OS, however, although two meta-analyses [28,29] disclosed a small but statistically significant improvement in OS with the addition of bevacizumab, another meta-analysis [27] failed to show the advantage of adding bevacizumab. These advantages, however, are accompanied by the cost of a slightly increased incidence of toxicities, including bleeding, thromboembolism, proteinuria, hypertension, neutropenia, and febrile neutropenia.…”

“…At least three meta-analyses demonstrated significantly improved ORR and PFS by adding bevacizumab to platinum-based two-drug chemotherapy for NSCLC [27][28][29]. With regard to OS, however, although two meta-analyses [28,29] disclosed a small but statistically significant improvement in OS with the addition of bevacizumab, another meta-analysis [27] failed to show the advantage of adding bevacizumab.…”

Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer

“…Furthermore, it is evident that both the PFS and OS are prolonged by treatment with platinum plus pemetrexed followed by continuous maintenance chemotherapy with pemetrexed alone [15] . In addition, the combined use of bevacizumab, anti-VEGF (vascular endothelial growth factor) antibodies prolongs the PFS in both the induction phase of platinum-doublet regimens and the continuous maintenance phase in the setting of nonsquamous NSCLC [16][17][18][19] . Recently, on the other hand, various types of molecular-targeted drugs have been developed in addition to conventional cytotoxic agents.…”