Ovarian cancer standard of care: are there real alternatives?

Abstract

Ovarian cancer remains a major issue for gynecological oncologists, and most patients are diagnosed when the disease is already advanced with a poor chance of survival. Debulking surgery followed by platinum-taxane chemotherapy is the current standard of care, but based on several different strategies currently under evaluation, some encouraging data have been published in the last 4 to 5 years. This review provides a state-of-the-art overview of the available alternatives to conventional treatment and the most promising new combinations. For example, neoadjuvant chemotherapy does not seem to be inferior to primary debulking. Despite its outcome improvements, intraperitoneal chemotherapy struggles for acceptance due to the heavy toxicity. Dose-dense chemotherapy, after showing an impressive efficacy in Asian populations, has not produced equal results in a European cohort, and the results of alternative platinum doublets are not superior to those of carboplatin and paclitaxel. In this setting, adherence to a maintenance therapy after first-line treatment and multiple (primarily antiangiogenic) agents appears to be effective. Although many questions, including the duration of maintenance treatment and the use of bevacizumab beyond progression, remain unanswered, new biologic agents, such as poly(ADP-ribose) polymerase (PARP) inhibitors, nintedanib, and mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors, have emerged as potential therapeutic options in the very near future. Based on the multiplicity of available strategies, the histological and molecular features of the tumor, in addition to patient's clinical condition and disease state, continue to gain importance in guiding treatment choices.

A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer

“…The foundation of current standard-of-care treatment for women diagnosed with EOC is cytoreductive (debulking) surgery and chemotherapy using a platinum-based combination regimen, most commonly the carboplatin-paclitaxel doublet. This strategy has largely reached a plateau of effectiveness in improving overall patient survival [7,8]. The continuing high mortality is associated, at least in part, with the fact that EOC is overwhelmingly diagnosed at an advanced stage.…”

“…More recently, an increased understanding of the biological and genomic complexity of EOC has prompted the exploration of molecularly targeted strategies designed to advance the field beyond the limitations of broadbased cytotoxic therapy [4,8]. In this regard, two new classes of targeted agents have been approved for EOC therapy in the last 5 years -angiogenesis inhibitors (bevacizumab) and PARP inhibitors (olaparib, rucaparib and niraparib) [23] -each of which selectively impact oncogenic pathways linked to ovarian tumorigenesis [24,25].…”

“…Furthermore, the clinical experience in advanced and relapsed EOC has shown that addition of a third cytotoxic compound to existing chemotherapeutic regimens results in increased toxicity without improving disease control [19][20][21]. Maintenance therapy with conventional cytotoxic agents has not demonstrated any meaningful OS benefit, yet cumulative toxicity associated with long-term chemotherapy has emerged as a major clinical concern [22].More recently, an increased understanding of the biological and genomic complexity of EOC has prompted the exploration of molecularly targeted strategies designed to advance the field beyond the limitations of broadbased cytotoxic therapy [4,8]. In this regard, two new classes of targeted agents have been approved for EOC therapy in the last 5 years -angiogenesis inhibitors (bevacizumab) and PARP inhibitors (olaparib, rucaparib and niraparib) [23] -each of which selectively impact oncogenic pathways linked to ovarian tumorigenesis [24,25].…”

FORWARD I: a Phase III study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer

“…It has been suggested that natural compounds, such as phytochemicals, may alleviate chemotherapy-induced side effects and therefore may be useful as adjuvants to standard treatment [10]; however, this field remains in its infancy. These measures underscore a critical need for innovative and effective therapeutic strategies for the management of advanced ovarian cancer.Due to an increased understanding of the biological and genomic complexity of EOC, recent progress has been made in the clinical application of molecularly targeted strategies designed to shift treatment away from broadbased cytotoxic use toward more tailored therapeutic interventions [11,12]. Approval of the angiogenesis inhibitor bevacizumab and the poly (ADP-ribose) polymerase inhibitors olaparib, rucaparib and niraparib [13,14], in both treatment and maintenance settings, highlights the degree to which targeted agents are presently impacting the treatment landscape for patients with advanced ovarian cancer.…”

“…Due to an increased understanding of the biological and genomic complexity of EOC, recent progress has been made in the clinical application of molecularly targeted strategies designed to shift treatment away from broadbased cytotoxic use toward more tailored therapeutic interventions [11,12]. Approval of the angiogenesis inhibitor bevacizumab and the poly (ADP-ribose) polymerase inhibitors olaparib, rucaparib and niraparib [13,14], in both treatment and maintenance settings, highlights the degree to which targeted agents are presently impacting the treatment landscape for patients with advanced ovarian cancer.…”