Bevacizumab Reduces Tumor Size, Improves Hearing in Vestibular Schwannomas

Bevacizumab is more efficacious compared with other targeted therapies for treating vestibular schwannomas, according to study findings published in the journal Neuro-Oncology Advances. 

One common manifestation of NF2-related Schwannomatosis (NF2-related SWN) is bilateral vestibular schwannomas, which can lead to hearing impairment. Some surgical treatments for symptomatic tumors can lead to permanent hearing loss, but other less invasive targeted treatments have potential for use. 

Researchers conducted a systematic review to determine the efficacy and safety of agents targeted at treating vestibular schwannomas. 

The researchers included studies that assessed patients with a confirmed NF2-related SWN diagnosis and measured hearing or radiographic response. Other inclusion criteria were patients not suited for surgery or radiotherapy and treated with targeted therapy. 

Studies in phase 0 or 1, with under 3 patients, not published in English, and published before 2008 were excluded from this study. 

To assess radiographic tumor volume, the researchers used the Response Evaluation in Neurofibromatosis and Schwannomatosis (ReiNS) criteria. They evaluated hearing response using recognition scores (WRS), with an increase in WRS indicating hearing response and a decrease indicating hearing decline.

The researchers defined radiographic response as greater than 20% decrease in tumor volume. In this study, progressive disease was characterized by a greater than 20% increase in tumor volume compared to baseline. 

The researchers collected data from the PubMed and EMBASE Ovid databases. A total of 16 articles were included in the final review, including 8 prospective and 8 retrospective studies. The targeted agents identified from these studies include bevacizumab, everolimus, lapatinib, erlotinib, axitinib, and a VEGF receptor vaccine.

A total of 10 studies including 200 patients had data regarding bevacizumab. Of these studies, 9 included hearing response to bevacizumab and showed that the responses ranged from 0% to 62%. Out of 108 participants, the hearing response rate was reported as 45% (95% CI, 36-54%). 

Hearing decline was evaluated in 7 studies with 116 participants and results ranged from 0% to 22%, with a pooled decline rate of 10% (95% CI, 4-15%).

The response rate to bevacizumab was reported in all studies, and results ranged from 12% to 100%. Out of 192 participants, the pooled response rate to bevacizumab was reported as 38% (95% CI, 32-45%). There were 8 studies with 168 participants that measured progressive disease with a pooled rate of 9% (95% CI, 5-13%).

The most common side effects of bevacizumab were proteinuria, hypertension, fatigue, mucositis, and menstrual abnormalities. 

Regarding the other targeted therapies, lapatinib had a 6% response rate and 31% hearing response. The only grade 3 toxicity in the lapatinib studies were delayed wound healing, which was reported in 4.8% of participants.

In addition, the VEGFR vaccine had a 29% response rate and 40% hearing response, with no grade 3 adverse events reported. 

“Compared to higher bevacizumab dosage (5 mg/kg/week), lower dosage (2.5 mg/kg/week) showed comparable efficacy and may be associated with reduced toxicity,” study authors stated. “Therefore, lower dosages of bevacizumab could be considered in the future treatment of VS in patients with NF2-related SWN.”

Study limitations are inclusion of many retrospective studies, leading to a potential heterogeneous study population and lack of data regarding dose scheduling.