A recent study concludes that both hypertension and proteinuria, which are considered to be interrelated with the pharmacological action of bevacizumab, have the potential to indicate greater likelihood of therapeutic efficacy.
Bevacizumab, an anti-vascular endothelial growth factor (anti-VEGF) treatment, can be used in combination with paclitaxel to treat advanced breast cancer, but hypertension and proteinuria are characteristic adverse events (AEs) associated with bevacizumab therapy. A proposed mechanism underlying bevacizumab-induced hypertension is the inhibition of VEGF, which results in decreased production of the vasodilator nitric oxide. Development of proteinuria has also been attributed to VEGF inhibition, which can decrease glomerular filtration and lead to protein leakage into urine.
A recent study in Japanese patients with breast cancer investigated whether these AEs could serve as predictors of treatment response to bevacizumab, and found that patients who developed hypertension and proteinuria early in their therapy had a stronger antitumor response.
The retrospective study, published in the Biological and Pharmaceutical Bulletin, included 19 patients with advanced, recurrent breast cancer treated in a single center in Japan between May 2012 to January 2016. Patients were observed from the beginning of therapy to 8 weeks after. During the observation period, 7 patients developed hypertension during the study period, while 12 did not; 7 patients developed proteinuria, and 12 did not.
No patients achieved a complete response, but in the group that developed hypertension, 100% achieved a partial response (PR), while 33.3% of the non-hypertensive group achieved a PR. Similarly, 100% of the group who developed proteinuria and 33.3% of the group who did not achieved a PR. According to the authors, these findings demonstrate a significantly stronger antitumor response in the 2 AE groups (P <.05).
Median progression-free survival (PFS) in the groups with and without hypertension were 355 days versus 147 days, respectively; median PFS for patients with and without proteinuria were 504 days versus 173 days, respectively.
The authors conclude that both hypertension and proteinuria, which are considered to be interrelated with the pharmacological action of bevacizumab, have the potential to indicate greater likelihood of therapeutic efficacy.
In order to control these AEs so that therapy can continue, say the authors, patients may need to be given appropriate antihypertensive medication. Proteinuria can, when of a high grade, require discontinuation of bevacizumab; however, the authors say that patients may continue to benefit from bevacizumab even after treatment discontinuation.
Tanaka H, Takahashi K, Yamaguchi K, et al. Hypertension and proteinuria as predictive factors of effects on bevacizumab on advanced breast cancer in Japan. Biol Pharm Bull. 2018;41(4):644-648. doi: 10.1248/bpb.b17-00605.