Tisotumab vedotin shows clinically meaningful OS improvement versus chemo for metastatic cervical cancer

Prof Ignace Vergote – UZ Leuven, Leuven, Belgium 

I was happy to present here at ESMO the randomised phase III study of tisotumab vedotin as second and third line in patients with recurrent metastatic cervical cancer. This group of patients who have had already fulvestrant chemotherapy maybe with IO drugs have a very poor prognosis with a PFS of less than three months and response rates of 5-6% by the addition of chemotherapy. This data presented a new way of treating these patients with an antibody drug conjugate, tisotumab vedotin, we call it just TV. Tisotumab vedotin is a monoclonal antibody targeted against tissue factor which is almost always expressed in cervical cancer and linked to vedotin which is a microtubule-disrupting agent.

What we did is we included patients who had had prior chemotherapy for recurrent disease and and, if available, also anti-PD-1. Then randomised between tisotumab vedotin IV versus chemotherapy investigator choice chemotherapy. We randomised 502 patients. The primary endpoint was overall survival and we also tested, of course, for PFS, objective response rate, quality of life, toxicity and so on.

We were happy to see that the primary endpoint was clinically and statistically significantly positive with a hazard ratio of 0.70, meaning a 30% decrease of death rate in these patients and also the progression free survival had a 33% decrease in that rate. So this must give this antibody drug which has significantly little side effects compared to the traditional chemotherapy but some typical side effects because it’s targeting tissue factor which is, for instance, present in the eyes. So we have to protect the eyes from conjunctivitis. But these side effects are reversible and usually only grade 1 or grade 2.

So we have a positive study and having this presented at the Presidential session, I think I’m convinced that this should be accepted as the new standard of care in second and third line cervical cancer.