Bringing new medicines to women with epithelial ovarian cancer: what is the unmet medical need?

Abstract

Background: Therapy for advanced epithelial ovarian cancer (OC) includes first line platinum/taxane-containing chemotherapy and re-treatment with platinum-containing regimens for disease recurrence in patients likely to respond again. Single-agent, non-platinum, cytotoxic agents are commonly used to treat patients resistant to platinum retreatment, but these agents are associated with dose-limiting toxicities and response rates below 20%.

Main body: Recent advances have led to novel targeted treatments for recurrent OC that offer opportunities to improve response rates and prolong progression-free intervals. However, they also add complexity to the process of selecting treatment for individual patients at different stages of the disease process. Advanced and recurrent OC is rarely cured. Multiple lines of platinum combinations, and nonplatinum chemotherapeutics eventually fail to achieve clinical benefit, thus other active and tolerable systemic therapies are needed. Consequently, the US Food and Drug Administration has created a mechanism for "accelerated approval" of new medicines in situations of high unmet medical need.

Conclusion: We review the clinical implications of recent key clinical studies in these settings and outline the path forward for study design and approval of novel therapeutics to treat recurrent OC.

Keywords: BRCA1/2; Ovarian cancer; PARP; Platinum-refractory.

Fig. 1

Definitions of Platinum-Refractory, Platinum-Resistant, Potentially Platinum-Sensitive, and Fully Platinum-Sensitive Ovarian Cancer. Patients with ovarian cancer are classified broadly in two main categories: “platinum-resistant” if the platinum-free interval (PFI) is less than 6 months, and “platinum-sensitive” if the PFI is at least 6 months. A more specific classification defines patients with ovarian cancer as “platinum-refractory” if disease progression occurs during chemotherapy or within 4 weeks after the last dose, “platinum-resistant” if the PFI is greater than 1 month and less than 6 months since last line of platinum-based therapy, “potentially platinum-sensitive” if the PFI is between 6 and 12 months, and “platinum-sensitive” if the PFI is more than 12 months

Fig. 2

Median Progression-Free Survival (a) and Overall Survival (b) Associated with Successive Lines of Chemotherapy (Versus no Treatment) in a Retrospective Analysis of Three Randomized Trials in Patients with Advanced Ovarian Cancer [19]. Data from Hanker et al. Ann Oncol. 2012;23:2605–12. Hanker et al. performed a retrospective, pooled analysis of three randomized, phase 3 studies of primary taxane-platinum-based chemotherapy. The analysis included 1620 patients for whom complete data were available. Responsiveness to platinum-containing regimens declined dramatically after 2 prior lines, even in patients who were initially platinum-sensitive [19]