In a phase II trial, responses were seen in 24% of patients with advanced or metastatic cervical cancer.

  • Major Finding: In a phase II trial, responses were seen in 24% of patients with advanced or metastatic cervical cancer.

  • Concept: The antibody–drug conjugate tisotumab vedotin targets Tissue Factor, overexpressed by many tumors.

  • Impact: This therapy warrants further investigation as there is currently no established second-line treatment.

Advanced-stage cervical cancer frequently recurs or progresses following standard-of-care first-line treatment, and there is no established effective second-line treatment for recurrent or metastatic disease. In an open-label, single-arm, phase II clinical trial, Coleman and colleagues used the antibody–drug conjugate tisotumab vedotin to treat 101 patients with advanced or metastatic squamous cell cervical carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma that had not responded to or recurred following admission of standard-of-care first-line therapies. Among all patients, the objective response rate was 24%, with 7% of patients exhibiting complete responses and 17% of patients exhibiting partial responses, and the median overall survival was 12.1 months. Interestingly, an exploratory biomarker analysis revealed no apparent dependence of response on membrane expression of the protein targeted by tisotumab vedotin (Tissue Factor; also known as CD142). This may be due to alternative mechanisms of action for tisotumab vedotin beyond expected direct cytotoxicity toward targeted cells, which may include bystander cytotoxicity or immunologic effects (e.g., immunogenic cell death, antibody-dependent cytotoxicity, or antibody-dependent phagocytosis). Despite implementation of an eye-care protocol due to the ocular treatment-emergent adverse events observed in the first-in-human trial of tisotumab vedotin, ocular adverse events remained common, affecting 53% of patients. However, most of these events were grade 1 or 2, limited to the surface of the eye(s), and temporary. One instance of fatal septic shock deemed by the investigators to be due to tisotumab vedotin occurred, indicating that further investigation or monitoring of this adverse event is justified, but the safety profile of tisotumab vedotin was otherwise as expected based on prior studies, with common adverse events including alopecia, epistaxis, nausea, and fatigue. In summary, the results of this trial indicate that further investigation of the use of tisotumab vedotin in this malignancy is warranted, particularly given that the prognosis of patients with advanced or metastatic cervical cancer that recurs or progresses after first-line treatment is poor due to a lack of effective second-line options.

Coleman RL, Lorusso D, Gennigens C, González-Martín A, Randall L, Cibula D, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2021;22:609–19.

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