Bevacizumab May Improve Responses in Pediatric Rel/Ref High-Risk Neuroblastoma

Bevacizumab may improve the efficacy of chemotherapy but increase toxicity when given to pediatric patients with relapsed or refractory, high-risk neuroblastoma, according to research published in the Journal of Clinical Oncology.

This phase 2 trial (ClinicalTrials.gov Identifier: NCT02308527) enrolled 160 patients with relapsed (n=93) or refractory (n=67) high-risk neuroblastoma. They had a median age of 5 years (range, 1-21 years) at baseline.

There were 80 patients who were not assigned to receive bevacizumab. This included 36 who were randomly assigned to receive temozolomide, 30 who were assigned to receive irinotecan plus temozolomide, and 14 who were assigned to topotecan plus temozolomide.

Of the 80 patients who were randomly assigned to receive bevacizumab, 34 were assigned to receive it in combination with temozolomide, 30 were assigned to receive bevacizumab plus irinotecan and temozolomide, and 16 were assigned to receive bevacizumab plus topotecan and temozolomide.

The median follow-up for survivors was 1.5 years. The objective response rate (ORR) was 26% for patients assigned to bevacizumab-containing regimens and 18% for patients who did not receive bevacizumab (risk ratio [RR], 1.52; 95% CI, 0.83-2.77; P =.17). This result met the predefined criterion for success (P <.2).

The 1-year progression-free survival (PFS) rate was 0.46% for the bevacizumab arms and 0.38% for the non-bevacizumab arms (hazard ratio [HR], 0.89; 95% CI, 0.63-1.27). The 1-year overall survival (OS) rate was 0.69% and 0.58%, respectively (HR, 1.01; 95% CI, 0.70-1.45).

The ORR was 20% in the irinotecan-temozolomide arms and 21% in the temozolomide arms (RR, 0.94; 95% CI, 0.47-1.89). The 1-year PFS rate was 0.53% and 0.30%, respectively (HR, 0.59; 95% CI, 0.39-0.90). The 1-year OS rate was 0.70% and 0.58%, respectively (HR, 0.65; 95% CI, 0.43-0.99).

The ORR was 27% in the topotecan-temozolomide arms and 23% in the temozolomide arms (RR, 1.22; 95% CI, 0.51-2.94). The 1-year PFS rate was 0.47% and 0.23%, respectively (HR, 0.59; 95% CI, 0.33-1.08). The 1-year OS rate was 0.60% and 0.52%, respectively (HR, 0.80; 95% CI, 0.44-1.45).

The most common grade 3 or higher adverse events were:

• Neutrophil count decrease — 51.5% overall, 30.5% in the bevacizumab arms, and 23.5% in the non-bevacizumab arms
• Platelet count decrease — 21% overall, 23% in the bevacizumab arms, and 21% in the non-bevacizumab arms
• Anemia — 16% overall, 14% in the bevacizumab arms, and 3% in the non-bevacizumab arms.

The researchers also found that “the addition of irinotecan is associated with more diarrhea and GI symptoms, whereas the addition of topotecan is associated with increased myelotoxicity. Whether one or the other toxicity profile is preferable remains a subject of debate and may vary from patient to patient.”

The researchers concluded that adding bevacizumab to temozolomide-based chemotherapy improved ORR and “appeared to show some improvement in PFS” when irinotecan or topotecan was added to temozolomide.

The researchers added that a potential interaction between irinotecan and bevacizumab might explain the better results they observed with bevacizumab plus irinotecan and temozolomide.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor