Amit M. Oza, MD, MBBS
Invited discussant of the FORWARD II trial,1Amit M. Oza, MD, MBBS, concluded that bevacizumab and mirvetuximab soravtansine was a “very well tolerated and effective” combination with “encouraging activity,” even in patients previously treated with bevacizumab and weekly paclitaxel. Dr. Oza is Head of the Division of Medical Oncology & Hematology, University Health Network/Mount Sinai, Professor of Medicine at the University of Toronto, Medical Director of the Cancer Clinical Research Unit, and Co-Director of the Drug Development Program at Princess Margaret Cancer Centre in Canada.
The study represents one of the emerging opportunities for overcoming resistance in ovarian cancer, according to Dr. Oza, in this case using folate receptor alpha (FRα) as a “precise homing target” for improving precision and potentially outcomes. Additionally, the approach aims to enhance the activity of two drugs—the antibody-drug conjugate mirvetuximab soravtansine and the antiangiogenesis agent bevacizumab—conceivably creating synergy that may impact cancer at the tumor microenvironment level.
“The results are intriguing and show a high level of activity in a platinum-agnostic group of patients,” Dr. Oza said. He noted the activity appears greatest in patients with high expression of FRα and slightly better still when those patients have platinum-sensitive recurrence.
In the previous FORWARD I trial,2 single-agent mirvetuximab soravtansine yielded a response rate of 24% and a median progression-free survival of 4.8 months, “which speaks to the improvement in terms of activity in conjunction with bevacizumab,” added Dr. Oza. In the current FORWARD II trial, activity was almost doubled, with patients who had high FRα expression demonstrating a response rate of 59% and a median progression-free survival of 9.7 months.
Focus of Future Research
Dr. Oza proposed several issues for clarification and future research: What is the prognostic impact of FRα? What is the best comparison to mirvetuximab soravtansine/bevacizumab for the group with high FRα expression? How active would weekly paclitaxel and bevacizumab be in the subset of high FRα expression, and should these two regimens be compared in a randomized trial? Finally, how should future trials incorporate aspects seen as important to patients—not only efficacy but tolerability and quality of life?
In the meantime, mirvetuximab soravtansine/bevacizumab demonstrated a high level of activity, which is particularly encouraging in that all patients had prior exposure to taxanes and 40% had prior treatment with bevacizumab, Dr. Oza pointed out. Additionally, 12 patients had received taxanes for recurrence, and 3 had prior treatment with weekly paclitaxel/bevacizumab. Activity was seen in those subsets of patients as well, he observed, “leading to the encouraging possibility that we can perhaps move beyond weekly bevacizumab and paclitaxel in recurrence.”
DISCLOSURE: Dr. Oza has held uncompensated relationships with Ozmosis Research.
REFERENCES
1. O’Malley DM, Oaknin A, Matulonis UA, et al: Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate, in combination with bevacizumab in patients with platinum-agnostic ovarian cancer: Final analysis. 2021 ASCO Annual Meeting. Abstract 5504. Presented June 7, 2021.
2. Moore K, Oza A, Colombo N, et al: FORWARD I (GOG 3011): A phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate, versus chemotherapy in patients with platinum-resistant ovarian cancer. Ann Oncol 30(suppl 5):v403, 2019.
