Role of antiangiogenic agents in first-line treatment for advanced NSCLC in the era of immunotherapy

Abstract

Background & objective “Anti-angiogenetic drugs plus chemotherapy” (anti-angio-chemo) and “immune checkpoint inhibitors plus chemotherapy” (ICI-chemo) are superior to traditional chemotherapy in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). However, in the absence of a direct comparison of ICI-chemo with anti-angio-chemo, the superior one between them has not been decided, and the benefit of adding anti-angiogenetic agents to ICI-chemo remains controversial. This study aimed to investigate the role of antiangiogenic agents for advanced NSCLC in the era of immunotherapy. Methods Eligible randomized controlled trials (RCTs) comparing chemotherapy versus therapeutic regimens involving ICIs or anti-angiogenetic drugs were included. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and rate of grade 3–4 toxicity assessment. R-4.3.1 was utilized to perform the analysis. Results A total of 54 studies with a sample size of 25,046 were finally enrolled. “Atezolizumab + Bevacizumab + Chemotherapy” significantly improved the ORR compared with “Atezolizumab + Chemotherapy” (Odds ratio (OR) = 2.73, 95% confidence interval (CI): 1.27–5.87). The trend also favored “Atezolizumab + Bevacizumab + Chemotherapy” in PFS and OS (hazard ratio (HR) = 0.71, 95% CI: 0.39–1.31; HR = 0.94, 95% CI: 0.77–1.16, respectively). In addition, “Pembrolizumab + Chemotherapy” and “Camrelizumab + Chemotherapy” significantly prolonged the PFS compared to “Bevacizumab + Chemotherapy” (HR = 0.65, 95% CI: 0.46–0.92; HR = 0.63, 95% CI: 0.41–0.97; respectively). Meanwhile, “Pembrolizumab + Chemotherapy” and “Sintilimab + Chemotherapy” yielded more OS benefits than “Bevacizumab + Chemotherapy” (HR = 0.69, 95% CI: 0.56–0.83; HR = 0.64, 95%CI: 0.46–0.91; respectively). Scheme between “Atezolizumab + Bevacizumab + Chemotherapy” and “Atezolizumab + Chemotherapy” made no significant difference (OR = 1.18, 95%CI: 0.56–2.42) concerning the rate of grade 3–4 toxicity. It seemed that ICI-chemo yielded more improvement in quality-adjusted life-year (QALY) than “Bevacizumab + Chemotherapy” in cost-effectiveness analysis. Conclusion Our results suggest that ICI-chemo is associated with potentially longer survival, better cost-effectiveness outcomes, and comparable safety profiles than anti-angio-chemo. Also, adding bevacizumab to ICI-chemo seemed to provide additional therapeutic benefits without adding treatment burden. Our findings would supplement the current standard of care and help the design of future clinical trials for the first-line treatment of patients with advanced NSCLC.

Efficacy and safety of apatinib plus chemotherapy vs. chemotherapy alone for the treatment of advanced‑stage non‑small cell lung cancer: A meta‑analysis

“…The high morbidity and mortality associated with advanced-stage NSCLC have brought an immense burden globally, particularly in China (2,5,6). Over the past decade, anti-angiogenetic treatments have seen notable progress in the treatment of advanced-stage NSCLC, which enhances the treatment response and prolongs patient survival with tolerable adverse events (33). Previously, bevacizumab was the main angiogenesis inhibitor for patients with advanced NSCLC (34).…”

Five years of safety profile of bevacizumab: an analysis of real-world pharmacovigilance and randomized clinical trials

“…Bevacizumab is a monoclonal antibody that targets VEGF. It blocks all isoforms of VEGF- A [ 4 ] and has shown clinical efficacy in a variety of cancers, including non-small cell lung cancer (NSCLC), advanced cervical cancer, glioblastoma, ovarian cancer and colorectal cancer [ 1 , 5 ]. In addition to the authorized indications, it has also shown good efficacy in the treatment of macular edema and renal cell carcinoma [ 2 , 6 ].…”

A pilot trial of consolidation bevacizumab after hypo‐fractionated concurrent chemoradiotherapy in patients with unresectable locally advanced non‐squamous non‐small‐cell lung cancer

“…There are ongoing trials evaluating the combination of bevacizumab and immunotherapy in NSCLC. A systematic review enrolling 54 randomized controlled trials suggests adding bevacizumab to chemotherapy‐immunotherapy may provide additional therapeutic benefits without increasing treatment burden 15 …”

“…A systematic review enrolling 54 randomized controlled trials suggests adding bevacizumab to chemotherapy-immunotherapy may provide additional therapeutic benefits without increasing treatment burden. 15 The aim of this trial was to determine the feasibility of incorporating consolidation bevacizumab into hypofractionated CCRT for unresectable LA-NS-NSCLC and to provide information for further investigating the combination of bevacizumab with consolidation immunotherapy. Conclusions: This pilot study met its goal of demonstrating the tolerability of consolidation bevacizumab after hypo-CCRT.…”