Bevacizumab in the Treatment of Advanced, Non-Squamous Non-Small Cell Lung Cancer: An Evidence-Based Approach

Abstract

Background: To assess the efficacy and safety of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC) on the basis of the two registrative trials [ECOG E4599 trial and BO17704 (AVAiL) trial]. Methods: A pooled analysis of the two trials was performed using a random effect model, and the results were summarized as number-needed-to-treat (NNT) and number-needed-to-harm (NNH). A 2-step analysis was performed. The primary analysis included only the patients treated with bevacizumab 15 mg/kg in the experimental arm, whereas the secondary analysis (with descriptive aim) included the patients treated with bevacizumab 15 mg/kg or those treated with bevacizumab 7.5 mg/kg in the experimental arm. The 1-year survival and 6-month progression-free rates were assumed as indexes of efficacy, and grade III–IV side effects were assumed as index of safety in both analyses. Results: 1,921 patients were potentially eligible for the pooled analysis and were included in the secondary analysis, whereas 1,576 patients were included in the primary analysis. A large heterogeneity was documented for both 6-month progression-free interval (I² = 88.164%, p = 0.004) and overall survival (I² = 73.541, p = 0.052). The absolute risk reduction of 1-year death and 6-month progression were 3.3% (95% CI = –6.5 to 13.2%, p = 0.507), with a NNT = 30; and 15.2% (95% CI = 0.07–29.6%, p = 0.04), with a NNT = 6 (both in favor of the bevacizumab-containing regimens), respectively. The absolute risk of treatment-related death was 2.4% (95% CI = 0.8–3.9%, p = 0.003), with a NNH = 41 against the bevacizumab-containing regimens; that of bleeding was 3.3% (95% CI = 1.6–4.9%, p < 0.001), with a NNH = 30; that of hypertension was 6.6% (95% CI = 4.6–8.6%, p < 0.001), with a NNH = 15; that of proteinuria was 2.1% (95% CI = 0.3–3.8%, p = 0.024), with a NNH = 47; that of neutropenia was 7.3% (95% CI = 3.2–11.4%, p < 0.001), with a NNH = 13; that of thrombocytopenia was 1.5% (95% CI = 0.2–2.7%, p = 0.021), with a NNH = 66. No significant differences were observed in the efficacy and the safety analysis when all the patients treated with bevacizumab 7.5 mg/kg and 15 mg/kg were included into the pooled analysis. Conclusion: Adding bevacizumab to standard chemotherapy in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC seems to favor a modest improvement in the main outcomes, with a significant worsening of the safety profile. These data suggest caution in the generalized use of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC.

BAP1 is a good prognostic factor in advanced non-small cell lung cancer

“…Adenocarinomas had lower BAP1 expression than squamous tumors (38% vs. 58.3%, respectively). Although non-squamous histology is a criterion for bevacizumab [17,18,19] as well as pemetrexed treatment [17,20,21], many patients with adenocarinoma are not sensitive to these drugs [22,23,24]. us, new targets for e ective drugs are always needed.…”

Evaluation of efficacy and safety for bevacizumab in treating malignant pleural effusions caused by lung cancer through intrapleural injection

“…In our study, we found that intrapleural injection of platinum chemotherapy drugs combined with bevacizumab reduced the incidence of chest pain (1.72 times) and mitigated the dyspnea of patients with MPE (3.07 times), compared with platinum chemotherapy drugs alone, which indicated that intrapleural injection of bevacizumab participation improved the QOL of patients with MPE. Previous study shows that adding bevacizumab to standard chemotherapy in the treatment of advanced non-squamous NSCLC seems to favor a modest improvement in the main outcomes [ 9 , 33 ] and bevacizumab significantly prolongs OS and progression-free-survival (PFS) when added to first-line platinum-based chemotherapy in patients with NSCLC [ 34 ].…”

Inhibitory Effects and Anti-Invasive Activities of Trehalose Liposomes on the Proliferation of Lung Carcinoma Cells

“…However, many clinical studies have indicated several limitations to the application in those therapies [3,4]. Although they kill tumor cells, chemotherapy damage normal cells.…”

“…Molecular targeted therapeutics for NSCLC have been developed such as bevacizumab [1] and gefitinib [2]. However, there have been severe side effects in those therapies [3,4]. Therefore, novel treatment methods with no side effects are required to improve quality of life for patients.…”