Cervical cancer is a type of cancer that affects millions of women every year. Despite improvements in screening and prevention, there is still a critical need for efficient treatment alternatives, especially for people with advanced or recurring diseases. Tisotumab vedotin, a ground-breaking targeted therapy, has emerged as a promising breakthrough in the fight against cervical cancer [1,2].
Understanding cervical cancer
Cervical cancer develops from abnormal cells lining the cervix, the lower portion of the uterus that connects to the vagina. It is the fourth most frequent type of cancer among women and is mostly caused by persistent infection with high-risk subtypes of the human papillomavirus (HPV), a sexually transmitted infection. Early detection is key to the successful treatment of cervical cancer, but instances that have spread or are recurrent present major complications. Also, no second-line treatment has been proven to be successful for advanced-stage cervical cancer, which frequently returns or metastases after receiving standard-of-care first-line therapies [1–3].
Tisotumab vedotin: A brief overview
Tisotumab vedotin is an antibody-drug conjugate that is being tested in clinical settings to treat a range of solid tumors. Tisotumab vedotin has consisted of a monoclonal antibody against human tissue factor, covalently linked to monomethyl auristatin E (MMAE), a strong cell division inhibitor. Monoclonal antibodies particularly target the tissue factor, which has been demonstrated to play a role in tumor growth, angiogenesis, and cancer metastasis. The tissue factor is overexpressed in a range of solid tumors, including cervical cancer.
The US Food and Drug Administration (FDA) granted tisotumab vedotin expedited approval in September 2021 for the treatment of adult patients with recurrent or metastatic cervical cancer with progression of disease on or following chemotherapy. Based on the tumor response rate and durability of response, this indication was approved [1–3].
Mechanism of action of tisotumab vedotin
Tisotumab vedotin works by a multi-step mechanism of action. After binding to the tissue factors on the surface of cancer cells, the antibody-drug conjugate is internalized by the tumor cell. Then the release of MMAE, a cytotoxic agent alters the microtubule network, prevents tumor cell proliferation, and induces apoptosis (programmed cell death). This targeted strategy improves the efficacy of the treatment while minimizing the impact on healthy cells and reducing systemic toxicity .
Clinical trials and efficacy of tisotumab vedotin
Patients with advanced or recurrent cervical cancer who have received all available standard treatment options have been included in clinical trials to assess the efficacy of tisotumab vedotin. Tisotumab vedotin exhibited clinically significant and long-lasting anticancer efficacy in pretreated patients with recurrent or metastatic cervical cancer in the innovaTV-201 and innovaTV-204 Phase I/II trials. According to the innovaTV-204 study, the objective response rate (the percentage of patients who experienced a significant decrease in tumor size) was around 24%, with 7% of patients achieving complete and 17% experiencing partial responses [2,3].
The effect of tisotumab vedotin in pre-treated recurrent or metastatic cervical cancer will be evaluated in the ongoing randomized, open-label Phase 3 innovaTV-301/ENGOTcx12/GOG-30xx trial. The phase 1b/2 experiment ENGOT Cx8/GOG 3024/innovaTV-205 is exploring tisotumab vedotin and other treatment combinations in the meantime. Tisotumab vedotin has a tolerable safety profile and potential anticancer efficacy. Additionally, the preliminary results demonstrated the viability of utilizing tisotumab vedotin in the first line and it provides an objective response rate of 55% and 41%, respectively, when combined with carboplatin or pembrolizumab in the first line .
Additionally, the findings of the innovaTV 206 study support the continued development of tisotumab vedotin as an effective second-line systemic treatment for patients with metastatic and recurrent disease that progresses during or after chemotherapy .
Safety profile and side effects of tisotumab vedotin
Although tisotumab vedotin exhibits promising efficacy, it is important to discuss its safety profile and possible side effects. In clinical trials, fatigue, alopecia (hair loss), nausea, epistaxis (nose bleeding), dry eye, conjunctivitis, and peripheral neuropathy (nerve damage) were the most frequently reported side effects. However, the majority of these adverse effects were manageable, and for many patients, the advantages of the therapy justified the associated risk [2–4].
Future implications and inference
Tisotumab vedotin offers a significant step forward in the treatment of cervical cancer providing new hope for patients with advanced or recurrent diseases. This cutting-edge therapy has the potential to enhance outcomes and improve the quality of life of patients with limited treatment options due to its targeted approach and encouraging clinical results. It is crucial to note that tisotumab vedotin is still undergoing clinical trials and has not yet obtained regulatory approval in all nations. However, preliminary data suggests its potential as a valuable addition to the therapeutic arsenal for cervical cancer.
1. Yonemori, K. et al. 'Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study'. Cancer Sci. (2022) 113(8), 2788–2797. DOI: 10.1111/cas.15443.
2. Hong, D.S. et al. 'Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer'. Clin Cancer Res. (2020) 26(6), 1220–1228. DOI: 10.1158/1078-0432.CCR-19-2962.
3. Bogani, G. et al. 'Tisotumab vedotin in recurrent or metastatic cervical cancer'. Curr Probl Cancer. (2023) 47(3), 100952. DOI: 10.1016/j.currproblcancer.2023.100952.
4. Arn, C.R. et al. 'Tisotumab Vedotin Safety and Tolerability in Clinical Practice: Managing Adverse Events'. J Adv Pract Oncol. (2023) 14(2), 139–152. DOI: 10.6004/jadpro.2023.14.2.4.