As reported in The New England Journal of Medicine by Ignace Vergote, MD, PhD, and colleagues, interim analysis of the phase III innovaTV 301 trial has shown improved overall survival and other efficacy outcomes with the antibody-drug conjugate tisotumab vedotin-tftv vs investigator’s choice of chemotherapy as second- or third-line treatment in patients with recurrent or metastatic cervical cancer.
The trial supported the April 2024 regular approval of tisotumab vedotin in patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
Ignace Vergote, MD, PhD
Study Details
In the open-label trial, 502 patients from sites in 27 countries were randomly assigned to receive tisotumab vedotin at 2.0 mg/kg every 3 weeks (n = 253) or investigator’s choice of single-agent chemotherapy (n = 249) consisting of either topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint was overall survival.
Overall Survival
At interim analysis, median overall survival was 11.5 months (95% confidence interval [CI] = 9.8–14.9 months) in the tisotumab vedotin group vs 9.5 months (95% CI = 7.9–10.7 months) in the chemotherapy group (hazard ratio [HR] = 0.70, 95% CI = 0.54–0.89, P = .004). Rates at 12 months were 48.7% (95% CI = 41.0%–55.8%) vs 35.3% (95% CI = 28.0%–42.7%), respectively.
Median progression-free survival was 4.2 months (95% CI = 4.0–4.4 months) in the tisotumab vedotin group vs 2.9 months (95% CI = 2.6–3.1 months) in the chemotherapy group (HR = 0.67, 95% CI = 0.54–0.82, P < .001); rates at 6 months were 30.4% vs 18.9%. A total of 127 patients in the tisotumab vedotin group and 108 patients in the chemotherapy group received subsequent anticancer therapy.
Objective response was observed in 17.8% vs 5.2% of patients (odds ratio = 4.0, 95% CI = 2.1–7.6, P < .001). Median response duration was 5.3 months vs 5.7 months.
Adverse Events
Grade ≥ 3 adverse events occurred in 52.0% of patients in the tisotumab vedotin group vs 62.3% of the chemotherapy group. The most common grade ≥ 3 adverse events occurring in either group were anemia (8.4% in tisotumab vedotin group vs 27.6% in chemotherapy group), urinary tract infection (4.4% vs 7.1%), and neutropenia (3.6% vs 13.4%). Serious adverse events occurred in 32.8% vs 39.3% of patients. Adverse events led to discontinuation of treatment in 14.8% vs 3.8% of patients. Treatment-related death occurred in two patients in the tisotumab vedotin group and one patient in the chemotherapy group.
The investigators concluded, “In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy.”
Dr. Vergote, of University Hospitals Leuven, Leuven, Belgium, is the corresponding author for The New England Journal of Medicine article.
Disclosure: For full disclosures of the study authors, visit nejm.org.
