Safety of Long-Term Therapy with Bevacizumab in Oncological Patients

VEGF Inhibition in Oncology Treatment 

Bevacizumab is a humanized recombinant monoclonal antibody that selectively binds to circulating vascular endothelial growth factor (VEGF), thus inhibiting its binding to VEGF receptors. This inhibition leads to the regression of the tumor vascular network.

It is used either as monotherapy or in combination with chemotherapy. Concomitant treatment with bevacizumab and chemotherapy has improved progression-free survival (PFS) and/or overall survival (OS) in patients with metastatic colorectal cancer, non-small cell lung cancer, metastatic breast cancer, metastatic renal cancer, ovarian or peritoneal carcinomas, cervical cancer, or multiform glioblastoma.

Extended Long-Term Treatment with Bevacizumab

Patients who were involved in previous clinical studies with bevacizumab and were eligible to continue at the end of these studies were included in an open long-term extension. Patients with disease progression or adverse events related to bevacizumab administration were excluded from the extension. Participants in the extension received bevacizumab at the same regimen as in the parent studies (7.5 or 15 mg/kg every 3 weeks; 5 or 10 mg/kg every 2 weeks intravenously).  

A total of 95 participants from 17 parent studies were included in the extension − the most being from the ROSIA study (indication ovarian cancer, NCT01239732, n = 41) and TAMIGA study (indication multiform glioblastoma, NCT01860638, n = 13). The majority of patients were women (70.5%), with a median age of 56 (23−81) years. The youngest patients on average were those with multiform glioblastoma, while the oldest were those with colorectal cancer.

Results

The overall median follow-up time in the extension was 20.7 months (95% confidence interval [CI] 14.9−27.6). The median follow-up time was longer for patients with breast cancer (45.4 months [95% CI 11.0−81.3]) and ovarian or peritoneal cancer (30.4 months [15.0−49.1]) compared to other indications. The median duration of bevacizumab therapy during the extension was 15.6 months (0−81.0), with a median total duration of treatment (parent study + extension) of 57.5 months (16.4−134.9).

The most common reasons for discontinuation of treatment were disease progression (n = 30) and the occurrence of adverse events during treatment (n = 25). A total of 27 participants did not complete safety monitoring (the most common reason was withdrawal of consent). At the end of the study, 14 patients were still on treatment (13 continued after the study ended, 1 stopped treatment based on the physician's decision). The longest treatment durations were experienced by 3 patients with breast cancer (≥ 10 years).  

Safety Profile

A total of 79 participants reported adverse events. The most common were proteinuria (n = 42), headaches (n = 15), asthenia (n = 15), hypertension (n = 12), nausea (n = 11), urinary tract infection (n = 10), and diarrhea (n = 10). The most common adverse events related to bevacizumab use were proteinuria and hypertension.

Grade ≥ 3 adverse events related to bevacizumab use were reported in 21 patients. No grade 4 or 5 adverse events related to bevacizumab were reported. A total of 17 patients experienced serious adverse events, and 4 patients died during the study extension (due to disease progression or unrelated adverse events).   

Conclusion

Safety data obtained from the extension confirm the good tolerability of long-term bevacizumab use in patients with various types of solid tumors, with a median treatment extension duration of nearly 5 years, and in some patients even ≥ 10 years.

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Source: Oza A. M., Dubois F., Hegg R. et al. A long-term extension study of bevacizumab in patients with solid tumors. Oncologist 2021; 26 (12): e2254−e2264, doi: 10.1002/onco.13971.