Bevacizumab: First-Line Therapy in Ovarian Cancer?
Dr. Swenerton. We can’t give the best advice to patients without a realistic awareness of the risks posed by disease and the outcomes realized with treatment. Tragically, the survival rates for women with ovarian cancer have improved little since the advent of platinum-based therapy more than 3 decades ago. For those with any macroscopic residuum, the risk for death from disease is greatest 2-3 years following diagnosis, the disease-specific 15-year survival is only 10%. Thus, for 9 of 10 women with advanced disease, treatment is palliative. To pretend otherwise creates false hopes and unfulfillable expectations. Worse, it can lead patients and clinicians to embark upon rigorous but ill-fated curative-intent regimens. As concluded at the most recent Helene Harris Memorial Trust Forum, “It is essential that measures of quality of life and symptom benefit are included with response and survival rates as primary end points in clinical trials that investigate palliative regimens.”
I agree that prolongation of PFS can be very useful clinically, particularly if it leads to a delay in recurrence of symptoms, a longer interval free of therapy, or a longer overall survival. However, neither of the first-line trials has yet shown such benefits for the broad, unselected spectrum of those with advanced disease. Our desperate need for substantial improvements in therapy must not drive us to indiscriminate use of a targeted agent, however heavily it’s promoted. The HHMT consensus emphasized, “The ceiling in efficacy that has been witnessed with all-inclusive phase III trials means that the priority should now be on type-specific (randomized) phase II trials based on sound scientific rationale.”
We’ve agreed that the data suggest that this drug is most effective, as it’s designed to be, in ameliorating the effects of excessive tumor-released VEGF. I’d endorse the carefully monitored use of bevacizumab in those faced with disease unlikely to respond to, or demonstrably not responding to, cytotoxic therapy -- this could include those with high-grade serous disease complicated by extensive effusions and those with clear cell and mucinous disease. Ideally, such treatments would be administered in the context of histotype-specific randomized phase 2 trials, designed to assess the relative utility of alternative antivascular agents, and include planned tumor resampling to clarify the resistance pathways that develop with this class of drugs.
Dr. Markman. In my opinion, both of you have provided a truly outstanding discussion of the complex issues surrounding the use of bevacizumab (and possibly other future targeted agents) in ovarian cancer. Thank you for your comments.
Pragmatic vs Indiscriminate Use
Dr. Swenerton. We can’t give the best advice to patients without a realistic awareness of the risks posed by disease and the outcomes realized with treatment. Tragically, the survival rates for women with ovarian cancer have improved little since the advent of platinum-based therapy more than 3 decades ago. For those with any macroscopic residuum, the risk for death from disease is greatest 2-3 years following diagnosis, the disease-specific 15-year survival is only 10%. Thus, for 9 of 10 women with advanced disease, treatment is palliative. To pretend otherwise creates false hopes and unfulfillable expectations. Worse, it can lead patients and clinicians to embark upon rigorous but ill-fated curative-intent regimens. As concluded at the most recent Helene Harris Memorial Trust Forum, “It is essential that measures of quality of life and symptom benefit are included with response and survival rates as primary end points in clinical trials that investigate palliative regimens.”
I agree that prolongation of PFS can be very useful clinically, particularly if it leads to a delay in recurrence of symptoms, a longer interval free of therapy, or a longer overall survival. However, neither of the first-line trials has yet shown such benefits for the broad, unselected spectrum of those with advanced disease. Our desperate need for substantial improvements in therapy must not drive us to indiscriminate use of a targeted agent, however heavily it’s promoted. The HHMT consensus emphasized, “The ceiling in efficacy that has been witnessed with all-inclusive phase III trials means that the priority should now be on type-specific (randomized) phase II trials based on sound scientific rationale.”
We’ve agreed that the data suggest that this drug is most effective, as it’s designed to be, in ameliorating the effects of excessive tumor-released VEGF. I’d endorse the carefully monitored use of bevacizumab in those faced with disease unlikely to respond to, or demonstrably not responding to, cytotoxic therapy -- this could include those with high-grade serous disease complicated by extensive effusions and those with clear cell and mucinous disease. Ideally, such treatments would be administered in the context of histotype-specific randomized phase 2 trials, designed to assess the relative utility of alternative antivascular agents, and include planned tumor resampling to clarify the resistance pathways that develop with this class of drugs.
Dr. Markman. In my opinion, both of you have provided a truly outstanding discussion of the complex issues surrounding the use of bevacizumab (and possibly other future targeted agents) in ovarian cancer. Thank you for your comments.