Revolutionizing Ovarian Cancer Treatment with Antibody-Drug Conjugates (ADCs)
In recent years, the pursuit of improving ovarian cancer treatments has led to better outcomes and new standards of care. However, many patients experience disease recurrence and develop resistance to chemotherapy, necessitating alternative treatments. Antibody-drug conjugates (ADCs) offer a promising targeted therapeutic approach that can expand treatment options and change ovarian cancer care.
Current Standard of Care for Ovarian Cancer
Traditional treatments for ovarian cancer involve surgery, chemotherapy, and targeted therapies. Initially, chemotherapy response rates are good, but most patients experience recurrence and chemoresistance. Recurrence limits treatment options and worsens prognosis due to systemic toxicity. Chemotherapy for recurrent disease typically results in response rates below 20%. Platinum-resistant ovarian cancer has poor outcomes with non-platinum chemotherapy, showing response durations of three to seven months and adverse effects like neutropenia, anemia, alopecia, thrombocytopenia, and neuropathy. These toxicities highlight the need for better-tolerated therapies.
ADCs: A Breakthrough in Ovarian Cancer Targeted Therapies
ADCs combine the precision of monoclonal antibodies with the cytotoxic effects of chemotherapy drugs. They target specific ovarian cancer cells that overexpress antigens, delivering cytotoxic agents directly to cancer cells while minimizing systemic toxicity and adverse effects.
Each ADC includes a biomarker-specific antibody, a cytotoxic payload, and a linker. The antibody targets cancer antigens, the linker releases the cytotoxic agent inside cancer cells, and the agent induces cellular death, sparing healthy cells. This targeted approach offers significant benefits to ovarian cancer patients, with ongoing research identifying new specific targets.
The Current Landscape of ADCs
ADCs are reshaping ovarian cancer treatment, especially for heavily pretreated patients. Their delivery system allows the use of highly potent chemotherapy agents, targeting tumor cells and sparing healthy ones.
Key developments include Mirvetuximab soravtansine (MIRV), the first FDA-approved ADC for ovarian cancer, targeting the FR-α biomarker. In clinical trials, MIRV showed a 42% overall response rate in platinum-resistant patients with high FR-α expression, significantly outperforming standard chemotherapy options. NaPi2b-targeting ADCs, such as lifastuzumab vedotin (LIFA) and UpRi, also show promising clinical potential, with improved response rates and drug delivery efficiency.
The Future of ADCs
Clinical trials for ADCs targeting biomarkers like FR-α and NaPi2b are underway, with over 30 ADCs targeting 20 additional biomarkers (including Cadherin 6, TROP2, mesothelin, and HER2) being investigated. Emerging data indicate a promising future for ADCs in treating ovarian cancer. Continued exploration of target antigens and ADCs is crucial for developing effective treatments for recurrent, platinum-resistant disease.
ADCs tend to be better tolerated than traditional chemotherapy, offering an alternative that limits systemic toxicity and maximizes patient well-being while improving response rates and outcomes.
