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The National Institute for Health and Care Excellence (NICE) has recommended tisotumab vedotin (Tivdak, Genmab) as an option for treating recurrent or metastatic cervical cancer that has progressed on or after systemic treatment in adults. 

The final draft guidance addresses what NICE describes as an unmet need for patients with advanced cervical cancer, who typically face limited therapeutic options beyond standard single-agent chemotherapy.

Disease Context

Cervical cancer develops when abnormal cells in the lining of the cervix grow uncontrollably and form a tumour, with human papillomavirus detected in 99.7% of cases. Recurrent or metastatic cervical cancer often affects young people who may have young children, leading to substantial disruption to quality of life, including physical and emotional exhaustion. 

For patients whose cancer progresses after first-line systemic treatment, limited treatment options are available, with current second-line treatment typically involving single-agent chemotherapy. The main aims of treatment in this setting are to relieve symptoms, improve quality of life, and extend survival.

How the Antibody-Drug Conjugate Works

Tisotumab vedotin targets tissue factor, which is highly expressed in several solid tumours, including recurrent cervical cancer. It consists of a tissue factor-directed human monoclonal antibody linked to the microtubule-disrupting agent monomethyl auristatin E, enabling targeted cytotoxic delivery directly to cancer cells.

Tisotumab vedotin is administered intravenously once every 3 weeks, offering a more convenient dosing schedule compared with weekly paclitaxel, one of the commonly used single-agent chemotherapy options in this setting.

Survival and Efficacy Data

The recommendation was based on evidence from the phase 3 InnovaTV 301 trial, which compared tisotumab vedotin with investigator's choice of single-agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer. The study enrolled patients who had received one or two prior lines of systemic treatment. 

Patients receiving tisotumab vedotin 2 mg/kg every 3 weeks achieved a median overall survival (OS) of 11.5 months compared with 9.5 months for those receiving chemotherapy, representing a 30% reduction in the risk for death. Median progression-free survival (PFS) was 4.2 months with tisotumab vedotin vs 2.9 months with chemotherapy, with a 33% lower risk for disease progression or death. The confirmed objective response rate was 17.8% in the tisotumab vedotin group compared with 5.2% in the chemotherapy group.

NICE concluded that clinical evidence shows tisotumab vedotin improved OS and PFS compared with single-agent chemotherapy in people with recurrent or metastatic cervical cancer who had received one or two prior lines of systemic treatment.

Safety Profile

While 98.4% of patients in the trial experienced at least one adverse event, grade 3 or greater events were lower in the tisotumab vedotin group (52.0%) than in the chemotherapy group (62.3%). Adverse events led to treatment discontinuation in 14.8% of patients. 

Ocular toxicity was common with tisotumab vedotin in the trial, with ocular treatment-emergent adverse events reported in 52.8% of patients compared with 6.3% in the chemotherapy arm. To manage this, a comprehensive eye-care protocol must be implemented, including ophthalmic examination before the first infusion, inspection of the eyes before each infusion, use of eye drops, cooling eye pads during infusion, and referral to an eye specialist if ocular signs or symptoms develop. Most eye-related toxicities improved or resolved over time.

Implementation and Access

The treatment will be funded in England within 90 days of final NICE guidance publication. Interim funding may be available through the Cancer Drugs Fund from the point of marketing authorisation or release of positive draft guidance, whichever is later, until routine commissioning begins.

The list price is £1995 per 40-mg powder vial, though the company has a commercial arrangement providing NHS access with a confidential discount. The estimated eligible patient population in England is approximately 117 people, according to the company estimate cited by NICE.

Patients will receive comprehensive information about potential side effects before starting treatment, and the NHS will need appropriate pathways to support ocular monitoring and ongoing care.