In clinical trials, 24% of patients achieved an objective response rate with tisotumab vedotin-tftv (TivdakTM) that lasted a median of 8.3 months, leading to the agent’s U.S. Food and Drug Administration September 2021 approval for use in adults with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
Mechanism of Action
Tissue factor–directed antibody bound to microtubule inhibitor conjugate monomethyl auristatin E (MMAE). MMAE disrupts the microtubule network of actively dividing cells, resulting in cell cycle arrest and apoptosis.
Adults with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy
2 mg/kg (maximum dose of 200 mg) as an IV infusion over 30 minutes every three weeks until patients experience disease progression or unacceptable toxicity
Premedicate with eye drops (corticosteroid and vasoconstrictor). Administer over 30 minutes through an IV line containing a 0.2 micron inline filter. Do not administer with other medications or as an IV bolus or push. Do not expose it to direct sunlight.
The drug has a boxed warning: “Tisotumab vendotin-tftv may cause changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Patients should obtain an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion.”
It has additional warnings for hemorrhage, pneumonitis, peripheral neuropathy, and embryo-fetal toxicity.
More than 25% of patients in clinical trials experienced decreased hemoglobin, lymphocytes, or leukocytes; fatigue, nausea; alopecia; epistaxis; hemorrhage; increased creatinine or prothrombin international normalized ratio; dry eye; prolonged activated partial thromboplastin time; diarrhea; or rash.
More than 15% of patients experienced decreased appetite, arthralgias, myalgias, periorbital and corneal adverse reactions, vomiting, constipation, abdominal pain, pruritis, pyrexia, neutropenia, decreased glucose, increase liver functions tests, alkaline phosphatase, or creatinine kinase.
Educate patients and caregivers about ocular care during therapy. Ensure patients have had an ocular exam and that eye drops were administered prior to each dose. Apply cold packs fully over the eyes, changing as needed to ensure that the eyes remain cold throughout the entire infusion.
Educate patients about and monitor for signs and symptoms of neuropathy, hemorrhage, and pneumonitis. Verify pregnancy status in patients of reproductive potential prior to administering therapy.
Drug-Drug and Drug-Food Interactions
Concomitant use with strong CYP3A4 inhibitors may increase unconjugated MMAE exposure and the risk of adverse reactions.
Patient and Caregiver Education
The medication may put you at risk for adverse ocular events; report any visual issues or concerns immediately. You will use eye drops pre- and postinfusion and must avoid using contact lenses.
Patients of reproductive potential should use effective contraception during treatment and for four months after the last dose. Do not breastfeed during treatment and for three weeks after the last dose.
Grade 3 or higher adverse reactions occurred in 69% of patients aged 65 or older and in 59% of patients younger than 65. Serious adverse reactions occurred in 54% of patients aged 65 or older and 41% of patients younger than 65.
Tisotumab vedotin-tftv is a hazardous drug requiring special handling and disposal procedures. It can cause fetal harm, impair male fertility, and pose serious adverse reactions during breastfeeding.
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