Targeted Anti-TF Antibody-Drug Conjugates in Advanced Cervical Cancer-Tisotumab Vedotin-Systematic Review

Background/Objectives: Cervical cancer (CC) is currently one of the leading causes of cancer-related mortality worldwide. Patients with advanced, recurrent, or metastatic CC, for whom treatment options are limited, are particularly at risk. Tisotumab vedotin (TV) is a first-in-class antibody-drug conjugate targeting tissue factor (TF), representing a promising therapeutic breakthrough. This systematic review aims to comprehensively evaluate the clinical efficacy, safety profile, and therapeutic potential of TV, both as monotherapy and in combination regimens, in patients with advanced cervical cancer. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Embase databases, as well as on the ClinicalTrials.gov website, for prospective clinical trials (Phases I-III) in accordance with the PRISMA 2020 guidelines. The search focused on original articles and studies published between 2019 and 2026. Four key clinical trial programmes (innovaTV 201, 204, 205, and 301), involving 548 patients, were selected. Quality assessment was performed using the Cochrane RoB 2.0 tool and the NIH tool for assessing the quality of "before-and-after" studies. Results: Objective response rates (ORR) with TV ranged from 17.8% in monotherapy to 65.8% in combination regimens, confirming its efficacy in treatment. In randomised Phase III trials, the use of TV improved overall survival compared to standard chemotherapy. Adverse effects characteristic of TV are primarily ophthalmic complications, peripheral neuropathy, and hemorrhagic events. These were managed through pre-established prophylactic and monitoring protocols. Combination therapies increased therapeutic efficacy but also raised the incidence of grade ≥ 3 adverse events occurring during treatment. Conclusions: TV offers new hope by changing the treatment algorithm for cervical cancer. As a targeted therapy, it provides an effective alternative to conventional chemotherapy in previously treated patients. It also has the potential for use in first-line multi-drug treatment regimens. Strict adherence to safety protocols is essential to minimise toxicity and ensure treatment continuity.