A new type of drug that targets chemotherapy directly to cancer cells reduces the risk of death from the most common type of bladder cancer by 30%, a phase III trial in the New England Journal of Medicine has suggested.
Researchers at Queen Mary University of London and Barts Health NHS Trust set out to investigate the efficacy of an antibody-drug conjugate, enfortumab vedotin, in 608 adult patients with locally advanced or metastatic urothelial cancer, who had previously been treated with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
Globally, urothelial cancer accounts for around 549,000 new cases of bladder cancer and 200,000 deaths each year, and is generally treated with chemotherapy.
Unlike conventional chemotherapy treatments, which can damage healthy cells, antibody-drug conjugates are targeted medicines that deliver chemotherapy agents directly to the cancer cells.
In the study, half of the patients were randomly assigned to receive enfortumab vedotin and half to receive chemotherapy. The primary end point was overall survival and median follow-up was 11.1 months.
The researchers found that overall survival was longer in the enfortumab vedotin group than in the chemotherapy group (12.88 months vs 8.97 months; hazard ratio for death, 0.70; 95% confidence interval [CI] 0.56 to 0.89, P=0.001).
Progression-free survival was also longer for those receiving the new drug at 5.6 months compared to 3.7 months for chemotherapy, and the overall percentage of patients with either complete or partial response was 40.6% in patients who received enfortumab vedotin compared with 17.9% of those who received chemotherapy.
Side effects were found to be manageable and similar to chemotherapy (93.9% in the enfortumab vedotin group compared to 91.8% in the chemotherapy group).
“This new type of drug has led to a survival advantage in bladder cancer, which has been difficult to achieve in this difficult disease,” said Tom Powles, professor of genitourinary oncology at Queen Mary University and lead UK researcher of the study.
“It reduced the death rate by 30% and beat chemotherapy in every setting, so this really is a big deal.”
Nisha Shaunak, lead pharmacist for oncology at Guy’s and St Thomas’ NHS Foundation Trust, said that data on this new type of systemic anti-cancer therapy was “potentially practice changing” for treating advanced urothelial cancer patients.
“For decades, few treatment options were available to treat this disease for which the prognosis remains poor. However, after introduction of immune checkpoint inhibitors a few years ago, it is encouraging to see that further progress has been made with enfortumab vedotin in this disease setting,” she said.
“Further clinical experience in the clinical setting will enable us to assess the real-world survival benefit of enfortumab vedotin.”
Shaunak added that “managing toxicities and measuring the impact on quality of life — outside the context of a clinical trial — will allow us to also understand its future place in therapy”.
The drug is already available in the United States after the Food and Drug Administration gave it accelerated approval, and is currently awaiting regulatory approval in the UK. Researchers say it could be available to NHS patients in a few months if it goes through the Early Access to Medicines Scheme.