The Safety and Effectiveness of Bevacizumab in the Treatment of Nonsquamous Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

Abstract

Objective. Bevacizumab was currently available for nonsquamous non-small-cell lung cancer (NSqNSCLC) patients and has been studied in several randomized controlled trials (RCTs) for treatment of these patients. This meta-analysis summarizes the most up-to-date evidences regarding the effects and adverse reactions of bevacizumab in the treatment of NSqNSCLC patients. Methods. The authors searched for RCTs from electronic database including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Experimental arm was defined as the bevacizumab-containing group and the control arm as the bevacizumab-free group. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse reactions were synthetically extracted. A protocol for this meta-analysis has been registered on PROSPERO (http://www.crd.york.ac.uk/prospero). Results. Ten RCTs that involved a total of 3134 patients were included. The experimental group was associated with significant superior ORR (RR 1.63, 95% CI 1.24 to 2.14, P < 0.001 ), OS (HR 0.90, 95% CI 0.82 to 0.99, P < 0.001 ), and prolonged PFS (HR 0.68, 95% CI 0.62 to 0.74, P < 0.001 ) compared to the control. No significant difference was observed regarding DCR (RR 1.13, 95% CI 0.99 to 1.30, P = 0.08 ). The experimental group showed higher rate of hypertension (RR 6.91, 95% CI 4.62 to 10.35, P < 0.00001 ) and hemorrhagic events (RR 3.07, 95% CI 1.78 to 5.30, P < 0.0001 ) than the control group. The experimental group showed lower rate of anemia (RR 0.72, 95% CI 0.55 to 0.96, P = 0.02 ) than the control group. No significant difference was observed regarding treatment-related adverse event grade 3-5 (TRAE3-5) (RR 1.23, 95% CI 0.99 to 1.53, P = 0.06 ), thrombocytopenia (RR 1.11, 95% CI 0.92 to 1.33, P = 0.29 ), and neutropenia (RR 1.11, 95% CI 0.88 to 1.40, P = 0.36 ). Conclusion. This meta-analysis showed that bevacizumab could increase ORR, OS, and prolonged PFS for treatment of NSqNSCLC patients. However, no significant improvement in DCR was observed and bevacizumab could increase the rate of hypertension and hemorrhagic events. Bevacizumab was an acceptable option for NSqNSCLC patients. This trial is registered with PROSPERO registration number: CRD42021226790.

Trends in antineoplastic drug use, cost and prescribing patterns among patients with lung cancer in nine major cities of China, 2016–2020: a retrospective observational study based on inpatient and outpatient hospital data

“…45 Although the cost of sintilimab was much lower than pembrolizumab, the prescriptions were also less as it was not included in clinical guidelines for lung cancer during the study period. 44 Several limitations of this study need to be acknowledged. First, given that the sample hospitals were often located in major metropolitan areas and the prescriptions were selected at random, the prescriptions in different regions might vary from 1 year to the next.…”

“… 45 Although the cost of sintilimab was much lower than pembrolizumab, the prescriptions were also less as it was not included in clinical guidelines for lung cancer during the study period. 44 …”

“…However, the number of prescriptions for other mAbs was modest due to the short introduction and supply time in China. Bevacizumab, ranked 14th in all antineoplastic drug prescriptions, was available for lung cancer treatment and added to the medical insurance list in China in 2017 16 44. Pembrolizumab showed good efficacy and safety for patients with advanced NSCLC; however, it was rarely used and not a cost-effective option in China due to its high price 45.…”

“…Pembrolizumab showed good efficacy and safety for patients with advanced NSCLC; however, it was rarely used and not a cost-effective option in China due to its high price 45. Although the cost of sintilimab was much lower than pembrolizumab, the prescriptions were also less as it was not included in clinical guidelines for lung cancer during the study period 44…”

Randomized, Phase II study of pemetrexed plus bevacizumab versus pemetrexed alone after treatment with cisplatin, pemetrexed, and bevacizumab in advanced non‐squamous, non‐small cell lung cancer: TORG (thoracic oncology research group) 1321

“…Many previous studies of advanced NSCLC have not shown that the addition of bevacizumab could prolong OS significantly 27,28 . On the other hand, some studies have shown that the addition of bevacizumab could prolong OS significantly 16,29 . These results may be because the proportion of patients who have overall survival benefits with bevacizumab is not very high.…”