Bevacizumab

MYL-1402O (Abevmy®, Lextemy®) is a biosimilar of the reference anti-vascular endothelial growth factor antibody bevacizumab. Abevmy® is approved for use in all indications for which reference bevacizumab is approved, including the treatment of non-small cell lung cancer (NSCLC) and other solid cancers. Lextemy® is approved for all indications as reference bevacizumab, except in recurrent ovarian cancer. MYL-1402O has similar physicochemical and pharmacodynamic properties to those of reference bevacizumab, and the pharmacokinetic similarity of the agents has been shown in healthy male subjects. MYL-1402O demonstrated clinical efficacy equivalent to that of reference bevacizumab in patients with non-squamous NSCLC. The tolerability, safety and immunogenicity profiles of MYL-1402O were consistent with those of reference bevacizumab. The role of reference bevacizumab in the management of solid cancers is well established and MYL-1402O provides an effective biosimilar alternative for patients requiring bevacizumab therapy.

Objective: The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent glioblastoma (GBM). We conducted a systematic review and meta-analysis to assess the efficacy of bevacizumab in recurrent GBM patients. Materials and methods: We searched electronic databases (Medline, Embase, and Web of Science) contrasting the bevacizumab with standard treatments up to May 2021. For the continuous outcomes of median progression-free survival (PFS) and median overall survival (OS), we summarized the mean difference (MD) as the effective index. We used relative risk (RR) to estimate the data with a random-effects model to get the outcomes of objective response rate (ORR), 12-month OS, 6-month PFS, and any mentioned adverse events. Results: A total of 807 patients in 5 RCTs included into our systematic review and meta-analysis. The results showed bevacizumab could provide benefits of the ORR (RR, 2.67; 95% CI: 1.14-6.26, p = 0.02), median PFS (MD, 1.12 months; 95% CI: 0.35-1.90 months, p = 0.005), but not the median OS (MD, -0.19 months; 95% CI: -1.37-0.99 months, p = 0.75). Whereas the rates of the secondary outcomes of interest were similar between the bevacizumab group and control group, including 6 month-PFS (RR, 1.23; 95% CI, 0.82-1.84, p = 0.32) and 12 month-OS (RR, 0.93; 95% CI, 0.79-1.09, p = 0.36). As for adverse events, patients with bevacizumab showed higher rates of grade 3/4 and any grade hypertension compared with those with standard treatments (RR, 3.71; 95% CI: 1.17-11.76, p = 0.03; RR, 2.68; 95% CI: 1.26-5.76, p = 0.01, respectively). Conclusions: This study provides clear proof of the beneficial effects of bevacizumab treatment in recurrent GBM patients. The only observed adverse event was grade 3/4 or any grade hypertension.

Background: PD-L1 expression on tumor cells is a marker of PD-1/PD-L1 antibody treatment efficacy for advanced non-small cell lung cancer (NSCLC). PD-L1 antibody (atezolizumab) prolongs overall survival (OS) compared with platinum doublet as first-line treatment for NSCLC with high PD-L1 expression. Bevacizumab enhanced cytotoxic agent and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor efficacy in non-squamous (NS)-NSCLC, and PD-1/PD-L1 antibodies in preclinical models. Methods: This single-arm phase II study investigated clinical benefits of adding bevacizumab 15 mg/kg to atezolizumab 1200 mg fixed dose in a first-line setting for advanced NS-NSCLC patients with PD-L1 expression ≥50% without EGFR/ALK/ROS1 alterations. Primary endpoint was objective response rate (ORR) assessed by central review committee. Secondary endpoints were progression-free survival (PFS), duration of response (DOR), OS, and safety. Results: Of 39 enrolled patients, 33 (84.6%) had stage IV NSCLC and 36 (92.3%) had smoking history. As of March 31, 2020, no patient had a complete response and 25 patients had a partial response (ORR=64.1%, 95% CI 47.18 to 78.80). Twelve-month PFS and OS rates were 54.9% (35.65 to 70.60) and 70.6% (50.53 to 83.74), respectively. The median DOR in 25 responders was 10.4 months (4.63-not reached). The median treatment cycle was 12 (1 to 27). Nineteen patients discontinued study treatment because of disease progression (N=17) or immune-related adverse events (AEs) (N=2) (sclerosing cholangitis or encephalopathy). There were 23 serious AEs in 12 patients, but no grade 4/5 toxicity. Conclusions: Atezolizumab with bevacizumab is a potential treatment for NS-NSCLC with high PD-L1 expression. Trial registration number: JapicCTI-184038.