Expert Opinion on Biological Therapy

Unmet needs in cervical cancer – can biological therapies plug the gap?

Cervical cancer remains one of the most common gynecologic malignancies worldwide. A disproportionate burden of cases occurs in developing countries due to inadequate screening and treatment. Even among patients adequately treated, in the presence of locally advanced or recurrent disease, outcomes tend to be poor. The introduction of biologic therapy into treatment has increased overall survival; however, a considerable opportunity still exists to improve current standards in treatment. Biologics have shown antitumor activity in multiple tumor types and are actively being pursued for the management of cervical cancer. In this article, we will discuss the historical evolution of biologic therapy in cervical cancer including use of angiogenesis inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, and vaccines. We will review how these therapies have been integrated into current treatment recommendations and discuss ongoing investigations intended to improve clinical outcomes. We also postulate on persistent gaps in care. Biologic therapies have had a tremendous impact on our current approach to managing cervical cancer. We anticipate that significant more research and development will be committed to the continued investigation of biologics in cervical cancer in an effort to improve a historically difficult to treat malignancy.

Targeting cervical cancer with anti-PD-1 antibodies: what is new?

Antibody-drug conjugates for the treatment of ovarian cancer

Ovarian cancer typically presents at an advanced stage and while initial chemotherapy response rates are favorable, a majority of patients experience recurrence with the subsequent development of chemoresistance. Recurrent, platinum-resistant disease is associated with a very poor prognosis as treatment in this setting is often limited by systemic toxicity. Antibody-drug conjugates (ADCs) are novel therapeutic agents designed to target antigens specific to ovarian tumor cells with direct delivery of cytotoxic agents to combat recurrent, platinum-resistant disease while limiting systemic toxicity. The basic structure and function of ADCs will be reviewed as well as the current data on ADCs under investigation in ovarian cancer. ADCs represent a promising class of targeted therapy in recurrent ovarian cancer with excellent response rates particularly when utilized as combination therapy. While mirvetuximab soravtansine is the only ADC that has been evaluated in a phase 3 trial, many other ADCs and trials are on the horizon. As the field of targeted therapy continues to evolve, continued development of target antigens and ADCs are likely to represent a key development in treatment of recurrent, platinum-resistant disease.

Novel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer

Antibody therapeutics for epithelial ovarian cancer

High-grade serous ovarian carcinoma (HGSC) is an aggressive subtype of epithelial ovarian carcinoma (EOC) and remains the most lethal gynecologic cancer. A lack of effective and tolerable therapeutic options and nonspecific symptoms at presentation with advanced stage of disease are among the challenges in the management of the disease. An overview of ovarian cancer, followed by a discussion of the current therapeutic regimes and challenges that arise during and after the treatment of EOC. We discuss different formats of antibody therapeutics and their usage in targeting validated targets implicated in ovarian cancer, as well as three emerging novel proteins as examples recently implicated in their contribution to adaptive resistance in ovarian cancer. Antibody therapeutics allow for a unique and effective way to target proteins implicated in cancer and other diseases, and have the potential to radically change the outcomes of patients suffering from ovarian cancer. The vast array of targets that have been implicated in ovarian cancer and yet the lack of effective therapeutic options for patients further stresses the importance of discovering novel proteins that can be targeted, as well as predictive biomarkers that can inform the stratification of patients into treatment-specific populations.

Review of emerging biological therapies for recurrent and advanced metastatic cervical cancer