Cervical cancer remains one of the most prevalent cancers worldwide. Despite the availability of preventative measures such as the HPV vaccine and advances in early detection, cervical cancer continues to be a significant health burden. If detected early, cervical cancer is one of the most successfully treatable cancers, but options are more limited for metastatic or recurrent disease.
Treatment for advanced or recurrent cervical cancer often involves a combination of surgery, radiation, and chemotherapy. The most commonly utilized first-line agents include cisplatin or carboplatin plus paclitaxel with bevacizumab with or without pembrolizumab. Second-line options were previously limited, but recent drug approvals provide novel therapeutic options for recurrent disease.
Antibody-drug conjugates (ADCs) have emerged as a promising option for recurrent cervical cancer. ADCs are a cancer treatment that combines the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapy agents via a chemical linker. The monoclonal antibody targets a specific protein on cancer cells, delivering the cytotoxic drug to its target. The linker ensures that the cytotoxic drug remains attached to the antibody until it reaches the cancer cells, minimizing toxicity to the healthy tissues. Many describe this cancer treatment as a “guided missile.”
Tisotumab vedotin (Tivdak®) is the first ADC approved for recurrent cervical cancer. This medication targets Tissue Factor (TF), a protein known to be increased in recurrent cervical cancer. In clinical trials, tisotumab vedotin significantly improved overall survival vs chemotherapy but had treatment-limiting side effects that are important to understand and manage. Tisotumab vedotin is known to commonly cause ocular (eye) toxicity, which can be severe. Ocular toxicity associated with tisotumab vedotin primarily manifests as dry eyes, redness, irritation, blurred vision, and in some cases corneal ulcers and vision loss. The mechanism behind these side effects is not fully understood but is thought to involve the off-target effect of the cytotoxic component on corneal and conjunctival cells.
The key to managing ocular toxicity is early detection. It is required that patients visit an eye specialist (optometrist or ophthalmologist) for eye examinations before starting the medication and before each cycle for the first nine cycles. Preventative measures, including the use of eye drops, can help mitigate the severity of ocular toxicity. The eye drops required during treatment consist of a prescription vasoconstrictor drop, a prescription steroid drop, and an over-the-counter lubricating eye drop.
Although Tissue Factor, the protein tisotumab vedotin targets, is found on cancer cells, it is also present on some normal cells. This can lead to other “off-target” side effects. Commonly reported side effects include decreased red blood cell counts and neuropathy (numbness/tingling in your hands or feet). These side effects typically do not occur immediately but rather in the days following treatment. Depending on the severity of these side effects, the prescribing oncologist may need to adjust, pause, or stop treatment until symptoms resolve.
Trastuzumab deruxtecan (Enhertu®), a different antibody-drug conjugate, may be used for patients with human epidermal growth factor receptor 2 (HER2)-expressing tumors. In order to receive this medication, HER2 expression must be confirmed via a diagnostic test. HER2 mutations occur in at least 5% of cervical cancers.
Before receiving trastuzumab dertuxtecan, patients should receive an echocardiogram, a type of heart scan to assess cardiac function. Trastuzumab deruxtecan can affect how well the heart is able to pump oxygen rich blood out into the body, thus patients should be assessed regularly throughout therapy to ensure it is safe for them to start or continue the medication. Additionally, trastuzumab deruxtecan has a warning for interstitial lung disease (ILD) and pneumonitis. Patients receiving this medication should inform their provider of any signs and symptoms, including cough, shortness of breath, fever, or other respiratory symptoms.
Antibody-drug conjugates represent a promising frontier in the treatment of cervical cancer, offering the potential for more targeted, effective, and less toxic therapies compared to conventional treatment. Although ADCs have their own unique side effect profiles, these effects are typically manageable. Early recognition, regular monitoring, and prompt intervention are essential in minimizing the impact of adverse events. As research continues, the potential of ADCs offers new hope in the fight against cervical cancer.
Learn more about cervical cancer treatment at Northside Hospital Cancer Institute.
