Real-World Use and Outcomes of Adjuvant Bevacizumab Therapy Prior to Regulatory Approval for Newly Diagnosed Ovarian Cancer

Use of adjuvant bevacizumab for newly diagnosed ovarian cancer in the United States before approval of the drug for this indication by the US Food and Drug Administration (FDA) substantially differed from such use in clinical trials, according to a recent analysis (Arch Gynecol Obstet. 2022; doi:10.1007/s00404-021-06282-6). The analysis revealed that many patients did not begin bevacizumab when initiating chemotherapy, and a much shorter course of bevacizumab than that used in clinical trials often was given. 

This retrospective cohort study used the IQVIA Pharmetrics Plus commercial claims database to identify women who had been newly diagnosed with ovarian cancer and had primary surgery or neoadjuvant chemotherapy before interval surgery b 2006 to 2018, the year that the FDA approved the use of adjuvant bevacizumab therapy for advanced ovarian cancer. On the basis of this data, they then calculated the rate of bevacizumab use and the relative frequency of hospital and emergency department (ED) admissions as well as the rate of treatment-related adverse events and time to initiation of second-line chemotherapy. 

As a result, the researchers determined that, of the nearly 9000 women who met the study parameters, 522 (6%) received bevacizumab. Furthermore, the rate of bevacizumab use increased significantly over time from 1.5% in 2006 to 7% in 2017 (P<0.001) and peaked in 2011 at 8.6%.

Use of bevacizumab was not affected by the number of comorbidities the patient had. However, bevacizumab was least frequently used in patients aged ≥70 years (in about 3%) and in the West (in 4.5%). More than a third of the women (35%) received bevacizumab for <3 months, and 16% continued to receive it for >13 months. 

Moreover, time from initiation of first-line chemotherapy to initiation of second-line chemotherapy was 22.6 months with adjuvant bevacizumab therapy vs 19.9 months without adjuvant bevacizumab therapy. “Interestingly, in patients who received bevacizumab per protocol, time to second-line chemotherapy appeared nearly 3 months longer, which is perhaps a proxy for progression free survival,” wrote Charlotte Gamble, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, and colleagues.

Their analysis found that adverse side effects related to bevacizumab use included hypertension in 15%, kidney damage in 7%, bleeding in 4%, venous thromboembolism in 2%, and fistula in 1%. “[A]dding bevacizumab to cytotoxic chemotherapy has a distinctly different set of toxicities related to its anti-angiogenesis mechanism of action,” noted Dr Gamble and team, adding that “concerns about survival benefit and toxicity may have translated into practice patterns.” Nevertheless, bevacizumab use was not associated with hospitalization or ED admission in their analysis.

“Efforts to align patterns of use with prescribing recommendations are needed to gain meaningful therapeutic benefit,” concluded Dr Gamble and colleagues, adding, “While patient–physician education and toxicity management may help to optimize use, further work to develop interventions to promote appropriate use of the drug are needed.”