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High-Dose Bevacizumab for Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas


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In a phase II trial reported in the Journal of Clinical Oncology, Plotkin et al found that high-dose bevacizumab induction therapy did not appear to produce better outcomes compared with lower-dose treatment in patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas. As noted by the investigators, bevacizumab at 7.5 mg/kg every 3 weeks has resulted in improvement in hearing in approximately 35% to 40% of such patients.

In the U.S. multicenter trial, 22 patients aged ≥ 6 years (median age = 32 years) with NF2 and progressive vestibular schwannoma–related hearing loss in the target ear received bevacizumab induction for 6 months at 10 mg/kg every 2 weeks; patients with stable or improved word recognition score (0% to 100% scale) received 18 months of maintenance bevacizumab at 5 mg/kg every 3 weeks. The primary endpoint was hearing response defined by word recognition score at 6 months.

Responses

Hearing response (≥ 21% improvement in word recognition score from baseline) was observed in 9 (41%) of 22 patients at 6 months, with responses being observed in 1 of 7 pediatric patients and 8 of 15 adults (P = .08). Radiographic response of vestibular schwannomas was observed in 7 of 15 adult patients (32%) at 6 months and in none of the 7 pediatric patients (P = .05).

KEY POINTS

  • Higher-dose bevacizumab did not appear to improve outcomes vs lower-dose treatment.
  • Hearing response was observed in 41% of patients at 6 months.

A biomarker study showed that high-dose bevacizumab was not associated with a significant decrease in free vascular endothelial growth factor; however, increases in plasma concentrations of carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell–derived factor 1α, and basic fibroblast growth factor were observed with high-dose bevacizumab.

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in three patients (13.6%; hypertension in two and abdominal pain in one). The most common treatment-related adverse events of any grade were hypertension (50%), irregular menstruation (46%, 6 of 13 female patients), fatigue (36%), headache (32%), and epistaxis (23%). One patient discontinued treatment due to colitis and intussusception.

Significant improvement in NF2-related quality of life on the NF2 Impact on Quality of Life questionnaire was observed in 32% of patients. Reduction in tinnitus-related distress on the Tinnitus Reaction Questionnaire was observed in 60% of patients.

The investigators concluded, “High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in quality of life during induction. Novel approaches using bevacizumab should be considered for children with NF2.”

Scott R. Plotkin, MD, PhD, of Massachusetts General Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Genentech and the Department of Defense. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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