Prof Christine Gennigens, a medical oncologist at CHU de Liège, conducted an interview with Prof Emeritus Ignace Vergote, a gynaecological oncologist at University Hospitals Leuven, who had the honour of presenting the innovative study, InnovaTV 301/ENGOT-cx12/GOG-3057, during the presidential session at ESMO 2023.
Prof Vergote commenced by elucidating the study’s design and rationale. This study represents a global, randomised, open-label, phase III clinical trial comparing tisotumab vedotin with the investigator’s choice of chemotherapy as the second or third-line treatment for recurrent or metastatic cervical cancer. It is important to note that patients in this cohort typically face a grim prognosis, as current standard chemotherapies exhibit limited efficacy, characterised by PFS rates of less than 3 months and response rates ranging from 5 to 6 percent. Tisotumab vedotin is an innovative antibody-drug conjugate comprising a tissue factor-directed human monoclonal antibody covalently linked to the microtubule-disrupting agent MMAE (monomethyl auristatin E).
The study included patients with either recurrent or primary metastatic disease who had already undergone one or two prior treatment regimens. Notably, 65% of patients received bevacizumab, a higher proportion compared to similar trials, and anti-PD-(L)1 therapy was administered to 28% of patients. Additionally, 81% of patients had received prior radiotherapy. In terms of histology, 63% of patients presented with squamous cell carcinoma, while the remaining cases involved adenocarcinoma or adenosquamous carcinoma.
For the primary endpoint, overall survival, the hazard ratio was 0.70, indicating a 30% reduction in the death rate with tisotumab vedotin compared to chemotherapy. The progression-free survival hazard ratio was 0.67 in the tisotumab vedotin arm, translating to a 33% reduction compared to chemotherapy. Moreover, the overall response rate was 18% for tisotumab vedotin and 5% for chemotherapy.
Prof Gennigens aptly pointed out that, despite these promising results, the absolute difference in median overall survival was merely 2 months. In response, Prof Vergote emphasised the importance of not fixating on medians, as they represent only a single point in the study’s data. Sometimes, even in highly favourable trials, the median values remain closely aligned, but the survival curves may diverge over time. What truly matters to patients is whether the treatment reduces their risk of death, so an analysis of the entire survival curve is crucial. For instance, at the 12-month mark, the survival rate was 49% with tisotumab vedotin compared to 35% with chemotherapy, reflecting a 14% difference.
Prof Vergote also highlighted another advantage of tisotumab vedotin for clinical practice, namely the remarkably short median time to treatment response, which stands at 1.4 months. This rapid onset of response renders it a valuable treatment option for symptomatic patients, especially when compared to immunotherapy, which typically requires more time to manifest clinical benefits.
In conclusion, Prof Vergote asserted that these results could potentially revolutionise clinical practice. Given the limited therapeutic options available for these patients, the emergence of an antibody-drug conjugate with demonstrated superiority in overall survival and other key endpoints is of immense significance. He also advocated for the reimbursement of this treatment in Belgium and throughout the European region.
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