Two New Targeted Therapies Available for Advanced Cervical Cancer

Christina S. Chu, MD

 

Until late 2021, patients with recurrent cervical cancer had limited options for treatment. Available treatments included standard chemotherapy regimens and the VEGF-inhibitor bevacizumab.

“Nobody was happy with the response rates patients were seeing with these agents,” said Christina S. Chu, MD, Interim Chief of the Division of Gynecologic Oncology at Fox Chase Cancer Center. “There was a great need for more effective second-line therapies.”

Then, in September 2021, the U.S. Food & Drug Administration (FDA) approved tisotumab vedotin-tftv, a tissue factor-directed antibody and microtubule inhibitor conjugate for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

“Tissue factor is upregulated in cancers, particularly in the endothelium, or the cells that line the blood vessels,” Chu said. “This conjugate drug also acts against microtubules, which form in cells and help cells the divide.”

The drug works by binding the antibody drug conjugate (ADC) to tissue factor (TF)-expressing cancer cells, followed by internalization of the ADC-TF complex and release of microtubule-disrupting agent monomethyl auristatin E (MMAE) via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death.

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The accelerated approval was based on a single-arm study of 101 patients assigned to 20 mg/kg intravenous tisotumab (up to 200 mg maximum) once every three weeks. The objective response rate was 24% with a median duration of response of 8.3 months.

“This drug gives comparable or better outcomes compared with other treatment options for this patient population,” Chu said. “This is a promising targeted therapy.”

Chu noted that tisotumab was approved with a Boxed Warning for ocular toxicity. An ocular event occurred in about 60% of patients assigned to the drug, she said. These included dry eyes, inflammation of the cornea, conjunctivitis, and more.

“The company is requiring people to have an eye exam before every cycle,” Chu said.

Specialists at Fox Chase are familiar with using tisotumab from their involvement in another clinical trial of the drug in patients with cervical cancer. Patients treated at Fox Chase are referred to a local eye group that understands how to manage cancer-related ocular toxicities.

Just a month after the approval of tisotumab, the FDA approved the PD-L1 inhibitor pembrolizumab in combination with chemotherapy with or without bevacizumab for patients with PD-L1 expressing persistent, recurrent, or metastatic cervical cancer. Pembrolizumab was also approved as a single agent for patients with PD-L1-expressing recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Chu said that about 30–35% of patients with squamous cell carcinoma of the cervix and about 20% of adenocarcinoma of the cervix will have PD-L1-expressing tumors. Patients whose disease is considered microsatellite instability (MSI)-high will also qualify for treatment with pembrolizumab.