Editorial: Making the most of every option in the treatment of ovarian cancer

Editorial:  Expert Review of Anticancer Therapy

‘…the limitation of relying solely on treatment-free interval cut-off points for therapy selection [in recurrent ovarian cancer] is nowadays regarded as a shortcoming’.

As the course of ovarian cancer is typically characterized by multiple remissions and relapses, careful strategic planning is required to optimize management. Therapeutic decisions taken at any given stage can impact on the efficacy and safety of future therapies. Newer cytotoxic regimens and targeted therapies such as antiangiogenesis agents and poly ADP ribose polymerase (PARP) inhibitors have led to improved outcomes for patients with recurrent ovarian cancer. However, a consequence of greater choice is the increased complexity of defining tailored therapeutic approaches, including optimal timing of administration and drug-sequencing strategies.
One of the main indicators of prognosis and probability of response to second- and subsequent-line therapy in recurrent ovarian cancer is the progression-free interval after the last dose of the preceding line of chemotherapy. Historically, patients have been classified as platinum-refractory (≤4 weeks before disease progression), platinum-resistant (<6 months), partially platinum-sensitive (6–12 months), and platinum-sensitive (>12 months) with respect to the interval between their last platinum application and a diagnosis of relapse [1 Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi24–32.[CrossRef], [PubMed], [Web of Science ®]]. The standard-of-care paradigm has been to treat platinum-resistant disease with non-platinum monotherapy and to treat platinum-sensitive disease with platinum combinations. However, this treatment paradigm has since been challenged and the limitation of relying solely on treatment-free interval cut-off points for therapy selection is nowadays regarded as a shortcoming. Although so-called platinum sensitivity may partially predict chemotherapy sensitivity, newer therapies do not necessarily follow this pattern; both antiangiogenesis agents and PARP inhibitors may act independently of the platinum-free interval. Furthermore, there are several profiles of so-called platinum-sensitive patients for whom platinum rechallenge is not the best approach. These include patients with a non-extensive platinum-free interval and patients not suited to receive platinum due to residual toxicities, hypersensitivity to platinum, or other reasons. For these patients, trabectedin + pegylated liposomal doxorubicin (PLD) can be regarded as a suitable non-platinum alternative [1 Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi24–32.[CrossRef], [PubMed], [Web of Science ®]]. Another potential positive impact of this strategy relates to the hypothesis that intercalation of trabectedin + PLD before platinum rechallenge may enhance the response to subsequent platinum by resensitizing tumor cells to platinum.
For many decades, a main objective in treating recurrent ovarian cancer has been to increase life expectancy while minimizing the toxic effects of chemotherapy. Modern treatment strategies offer potential to improve overall survival, a stubbornly elusive therapeutic goal until recently.