When more is better: bevacizumab treatment for patients with ovarian cancer

From the Liao Group, Breast and Ovary Cancers Research Program, Cancer Consortium

Ovarian cancer comprises a group of different cancers that can form in the ovaries, fallopian tubes, or the peritoneum. For those patients within this population with aggressive disease, continuous efforts are ongoing to determine optimum treatment trajectories, which often involves combination treatments, with the goal of prolonging overall survival and improving quality of life. Targeted therapies are designed to attack and eliminate specific cell types and one therapy in particular, a monoclonal antibody termed bevacizumab, is frequently utilized in the ovarian cancer space. Bevacizumab targets VEGF – a growth factor that can promote tumor angiogenesis in ovarian cancer - blocking its effects and reducing tumor growth. Of relevance, is the role bevacizumab may play in disease maintenance, continuous use is linked to stability of reduced disease burden, with discontinuation of the therapy associated with tumor regrowth in other cancer types. However, heterogeneity exists with respect to the timing of its usage along the care continuum (at what timepoint and stage in recurrent disease) and insight is needed into how this might impact the patient population.

Recently, Dr. Talayeh Ghezelayagh, a Gynecologic Oncology Fellow at the University of Washington and Dr. John Liao, Associate Program Leader of the Breast and Ovary Cancers Research Program at the Cancer Consortium, undertook a retrospective study of patients with recurrent ovarian cancer to determine whether timing of receipt of bevacizumab and the duration (how many cycles the patient received) impacted overall survival. Their work, recently published in European Journal of Gynaecological Oncology, reveals that receipt of bevacizumab earlier in disease recurrence, i.e., after the first or second recurrence event, allowed for additional cycles to be administered which improved overall survival for patients. “Bevacizumab is now a standard component of ovarian cancer treatment in the front line or recurrent setting but data does not really exist to guide clinicians on when it should optimally be used in a patient's cancer care to have the maximal benefit. Should it be used earlier with a first or second recurrence and does it have the same benefit if employed later on? By combining data from four comprehensive cancer programs and with support from the Fred Hutch Cancer Center for multi-disciplinary and multi-institutional research, we were able to examine that question in more detail,” said Dr. Ghezelayagh.

The authors compiled a study population of patients with ovarian cancer who had been treated with bevacizumab over a ten-year period at Northwestern University, Swedish Cancer Institute in Seattle, University of Pennsylvania, and University of Washington. Key variables in their retrospective analysis of this patient data were the number of chemotherapy regimens received by the patient prior to bevacizumab, the time from diagnosis of disease to treatment with bevacizumab, and how many cycles of bevacizumab the patient received. By assessing these data outcomes in univariate and multivariate statistical models, the authors aimed to determine both the optimum timing for administration of bevacizumab and the optimum number of cycles which would confer the most benefit to patients.

Six or more cycles of bevacizumab treatment improves overall survival for patients with ovarian cancer.
Six or more cycles of bevacizumab treatment improves overall survival for patients with ovarian cancer. Image from original article. This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

After defining their patient population, the authors aimed to understand the factors involved in determining the number of cycles of bevacizumab received by a patient. When grouping patients by those who received ≥ 6 cycles of bevacizumab compared to those who received ≤ 6 cycles, the authors noted that while there were no significant differences in some clinical characteristics such as stopping treatment due to toxicity or use of neoadjuvant chemotherapy between groups, patients who received ≥ 6 cycles of bevacizumab were more likely to have started bevacizumab treatment earlier, after their first or second recurrence, and were less likely to have primary platinum resistance. These findings remained constant in both their univariate and multivariate statistical models, with the authors confirming a significant association between primary platinum resistance and receiving a reduced number of bevacizumab cycles, and a significant association between starting treatment after the first/second recurrence and receiving ≥ 6 cycles of bevacizumab.

The authors next asked, what is the impact of cycle number on overall survival or progression free survival? Notably, they observed increased overall survival from diagnosis in those patients who received ≥ 6 cycles of bevacizumab. Further, patients who began treatment with bevacizumab at an earlier stage in recurrence, after the first or second recurrent event, had improved overall survival outcomes than those patients who began treatment after multiple recurrences. Taken together these findings suggest that timing (when to begin bevacizumab treatment) and the duration (number of cycles) are key considerations for improving overall survival in patients with recurrent ovarian cancer. “Our data suggests that using bevacizumab after the first or second recurrence has a survival advantage and might be prioritized in those ovarian cancer patients,” summarized Dr. Ghezelayagh.

The Breast and Ovary Cancers Research Program at the Cancer consortium “fosters collaborative research and team science both within our institution and across institutions, locally and nationally. The Breast and Ovary Cancers Research Program served as a model for how we approached our scientific question and the collaborations we made were crucial to completing this project,” concluded Dr. Liao. 

This work was supported by funding from the National Cancer Institute of the National Institutes of Health, and the Feuer Research Fund for Ovarian Cancer.

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Renata R. Urban, Heidi J. Gray, Barbara Ann Goff, James Y. Dai, and John B. Liao contributed to this work.

Ghezelayagh TS, Wu ES, Barber EL, Dao MD, Zsiros E, Urban RR, Gray HJ, Goff BA, Shah CA, Neubauer NL, Dai JY, Tanyi JL, Liao JB. Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study. Eur J Gynaecol Oncol. 2023 Feb;44(1):17-25. doi: 10.22514/ejgo.2023.002. Epub 2023 Feb 14. PMID: 36874058; PMCID: PMC9980410.