“The phase III ENGOT/GCIG study1 proved to be negative, with no advantage seen with the extension of bevacizumab treatment,” said the abstract’s invited discussant, Carol Aghajanian, MD, Chief of the Medical Gynecologic Oncology Service at Memorial Sloan Kettering Cancer Center, New York.
Dr. Aghajanian noted the importance of stratifying patients according to whether they had no gross residual disease or residual/stage IV disease. “This has been postulated as the selection criterion for bevacizumab use, based on ICON7,” she added.2
Benefit of Bevacizumab: ‘Across Entire Spectrum of Disease’
Although the longer duration of bevacizumab did not translate into better outcomes, the role of this drug in advanced ovarian cancer is indisputable. As Dr. Aghajanian pointed out, it has been shown in phase III trials to have activity across all disease states, “from upfront therapy to platinum-sensitive recurrence to platinum-resistant recurrence.” Unlike platinum agents and PARP (poly [ADP-ribose] polymerase) inhibitors, where platinum sensitivity is a biomarker of response, “bevacizumab adds clinical benefit across the entire spectrum of disease,” noted Dr. Aghajanian.
Carol Aghajanian, MD
“It also appears that bevacizumab is not subject to resistance in the same way that agents like PARP inhibitors are,” she continued, describing how bevacizumab has been shown to maintain benefit in platinum-sensitive recurrence, even in patients who received it as part of upfront therapy. The recent study by the MITO16b/MANGO-OV2/ENGOT-ov17 group3 tested the value of continuing bevacizumab beyond disease progression after first-line treatment with bevacizumab; most patients had completed upfront therapy, but some were re-treated when disease recurred during maintenance. Patients receiving a chemotherapy doublet alone had a median progression-free survival of 8.8 months; this rose to 11.8 months with chemotherapy plus bevacizumab (hazard ratio = 0.51; P < .0001).
“Thus,” Dr. Aghajanian emphasized, “although this presentation did not show any additional benefit from extending the duration of bevacizumab with upfront therapy, we can achieve benefit from bevacizumab by repeat treatment in the recurrent setting.”
DISCLOSURE: Dr. Aghajanian has served as a consultant or advisor to AbbVie, AstraZeneca/Merck, Eisai, Mersana Therapeutics, Repare Therapeutics, Roche, and Roche/Genentech; and has received institutional research funding from AbbVie, AstraZeneca, Clovis Oncology, and Genentech/Roche.
REFERENCES
1. Pfisterer J, Joly F, Kristensen G, et al: Optimal treatment duration of bevacizumab combined with carboplatin and paclitaxel in patients with primary epithelial ovarian, fallopian tube, or peritoneal cancer: A multicenter open-label randomized 2-arm phase 3 ENGOT/GCIG trial of the AGO Study Group, GINECO, and NSGO (AGO-OVAR 17/BOOST, GINECO OV118, ENGOT Ov-15, NCT01462890). 2021 ASCO Annual Meeting. Abstract 5501. Presented June 7, 2021.
2. Perren TJ, Swart AM, Pfisterer J, et al: A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484-2496, 2011. Erratum: N Engl J Med 366:284, 2012.
3. Pignata S, Lorusso D, Joly F, et al: Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: A randomised, phase 3 trial. Lancet Oncol 22:267-276, 2021.
