When determining the optimal treatment for a patient with platinum-resistant ovarian cancer, it is important to know which prior therapies were administered and whether serious toxicity occurred, states Thomas Herzog, MD. Additionally, it is important to take into consideration future toxicities, treatment expectations, and the convenience of the dosing schedule with every line of therapy, adds Robert L. Coleman, MD.
The FDA’s emphasis on demonstrating overall survival (OS) benefit for investigational treatments may have contributed to an 8-year gap in the development of novel ovarian cancer therapies, comments Herzog. The lengthy post-progression survival that has been seen in ovarian cancer makes proving an OS advantage difficult, notes Herzog. To show an OS advantage, the study would need to be lengthy, require the enrollment of thousands of patients, and would carry a very high cost. For these reasons, says Herzog, investigators have begun to explore surrogate endpoints.
The recent FDA approvals of ovarian cancer treatments olaparib, gemcitabine in combination with carboplatin, and bevacizumab in platinum-resistant disease, were not based on OS, says Angeles Alvarez Secord, MD. Other endpoints, such as progression-free survival (PFS), objective response rate, and improvements in quality of life and symptoms, were taken into account. Challenges associated with using these endpoints include determining what type of quality of life primers to use.
Using PFS as a primary endpoint should show sufficient prolongation of tumor stabilization and disease control to be considered clinically meaningful, comments Bradley J. Monk, MD. The investigational treatment should also be associated with a tolerable level of adverse events and ideally should demonstrate an improvement in patient reported outcomes with no detriment in OS.
Defining adequate prolongation of PFS varies depending on the disease setting, notes Monk. For example, asymptomatic patients who require frontline maintenance may need more benefit than patients with platinum-resistant disease, where bevacizumab is now labeled after establishing a PFS benefit of 3.4 months compared with chemotherapy.