The Future of Ovarian Cancer Treatment with Antibody-Drug Conjugates (ADCs)

In recent years, the relentless pursuit of improving treatment for ovarian cancer has led to better outcomes and created new standards of care for ovarian cancer. However, following successful rounds of chemotherapy, many ovarian cancer patients will experience disease recurrence and develop resistance, necessitating alternative treatment. Antibody-drug conjugates (ADCs) represent one type of targeted therapeutic modality that offers opportunities to expand biomarker-based treatment options and revolutionize the landscape of ovarian cancer care.

Current Standard of Care for Ovarian Cancer

Ovarian cancer treatments have traditionally involved a combination of surgery, chemotherapy and targeted therapies. Initial chemo response rates are favorable, but most patients develop disease recurrence with chemoresistance. When cancer comes back, the available treatment options become more limited and the prognosis is often poor due to systemic toxicity. Most patients treated with chemotherapy for recurrent disease experience response rates under 20%. For those with platinum-resistant ovarian cancer, non-platinum chemotherapy has been associated with response durations limited to about three-seven months. In addition, these agents may also lead to adverse effects such as neutropenia, anemia, alopecia, thrombocytopenia and neuropathy. These associated toxicities limit the chemotherapy’s applicability, leaving a great unmet need for novel therapies that are better tolerated and effective for recurrent ovarian cancer and other gynecologic malignancies.

The available arsenal of treatment options has expanded as cancer care teams continue to research new pathways to healing, with novel therapies such as antibody-drug conjugate (ADCs) emerging as a transformative addition.

ADCs: A Breakthrough in Ovarian Cancer Targeted Therapies

ADCs are a breakthrough in targeted therapies for ovarian cancer, combining the targeted precision of monoclonal antibodies with the potent cytotoxic effects of chemotherapy drugs. They represent a promising new class of treatment with less toxicity than standard chemotherapy and excellent response rates.

These ADCs are designed to target specific ovarian cancer cells that overexpress antigens, treating them with an optimal direct delivery of high-potency cytotoxic agents to effectively combat treatment-resistant disease while limiting overall system toxicity and minimizing adverse effects.

Each ADC is carefully and uniquely engineered with a biomarker-specific antibody, cytotoxic payload, and linker. First, the antibody targets specific cancer antigens. Then, after internalization of ADC to specific cancer cells, the linker will be released and finally, the cytotoxic agent will induce cellular death in the tumor cell only.

Utilizing a fascinating science, ADCs provide a considerable benefit to ovarian cancer patient populations and will continue to do so as researchers learn more about the specific targets found on these tumor cells that do not exist in normal cells.

The Current Landscape of ADCs

The introduction of ADCs is shifting the landscape of ovarian cancer treatment approaches for heavily pretreated ovarian cancer patients. The novel delivery system of ADCs allows cancer care teams to use highly potent chemotherapy agents that are too strong to use in isolation because of their toxicity. It ensures that the powerful chemotherapeutic agents are only released once safely inside the tumor cell to spare healthy cells.

The two primary targets in ADC development today include the FR-α and NaPi2b biomarkers. Mirvetuximab soravtansine (MIRV) was the first FDA-approved ADC to treat ovarian cancer, a potential option among the 60% of serious epithelial ovarian cancers with a high FR-α expression. In one MIRV study, patients with platinum-resistant epithelial ovarian cancer whose tumors had high FR-α expression and who had been treated with up to three prior lines of therapy saw an overall response rate of 42% after MIRV was administered – significantly higher than response rates for standard chemotherapy options. It was also well tolerated among patients, with only 7% discontinuing use due to adverse effects.

Two ADCs targeting NaPi2b have been investigated in an early phase and show promising clinical potential. The use of lifeastuzumab vedotin (LIFA) showed a 36% response rate versus 14% in patients treated with pegylated liposomal doxorubicin. The other NaPi2b-targeting ADC, UpRi, is a first of its kind, utilizing a unique design that improves drug concentration at the tumor and is hypothesized to require a lower dose or less frequent administration.

The realm of ADCs in ovarian cancer treatment is evolving rapidly. Targeted therapies and existing ADCs offer newfound hope to patients as they continue to be explored in clinical trials and integrated into treatment regimens.

The Future of ADCs

Clinical trials for certain ADCs are already underway, as explored above with the targets FR-a and NaPi2b. Now, more than 30 ADCs targeting 20 other biomarkers (including Cadherin 6, TROP2, mesothelin, and HER2) are being investigated through clinical trials in the field, both independently and in combination with others.

Emerging data from recent and current studies indicate a promising future for ADCs in treating ovarian cancer. The continued exploration of target antigens and ADCs is critical to finding new ways to treat recurrent, platinum-resistant disease that presents differently in each patient.

While ADCs have their unique adverse effects, they tend to be better tolerated by patients than chemotherapy. As cancer care teams aim to avoid treatments that are worse than the disease, ADCs represent a hopeful alternative that limits system toxicity and maximizes patient well-being while producing better response rates and outcomes.

ADCs: Precision Meets Potency

In the dynamic landscape of ovarian cancer treatment, treating physicians know that this patient population needs more options. Every tumor has a unique profile, so the more antigens are studied, and the more ADCs are developed, the more available options each patient will have.

ADCs present a solution where precision meets potency, allowing our cancer experts to deliver highly toxic payloads to cancer cells only, sparing healthy cells and limiting toxicity in the patient overall. As more clinical trials unfold and new research propels the field forward, Moffitt will remain at the forefront of these innovative therapies and provide our patients with the most effective treatment options. We continue to collaborate with referring providers to deliver the best experience and ensure our patients feel fully supported at every step of their cancer journey.

If you’d like to refer a patient to Moffitt, complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.