Combination of pembrolizumab and enfortumab vedotin approved for the treatment of bladder cancer

Merck and Pfizer have simultaneously announced that Health Canada has approved the combination of two of their drugs for the treatment of bladder cancer. The combination of Keytruda® (pembrolizumab), manufactured by Merck, and Padcev® (enfortumab vedotin), produced by Pfizer, is indicated for “the treatment of adults with locally advanced, inoperable or metastatic urothelial cancer who have never received systemic therapy.”Urothelial cancer accounts for 90% of all bladder cancers. It starts in the urothelial cells lining the urethra, bladder, ureters and renal pelvis, and can rapidly metastasize. It is estimated that approximately 12,300 Canadians will be diagnosed with bladder cancer in 2024, including an estimated 2,600 deaths, making it the fifth most common type of cancer in the country and the ninth leading cause of cancer-related death.In 11% of cases, urothelial cancer is already locally advanced or metastatic at the time of diagnosis. It may then stop progressing, regress or even disappear in response to current treatment options, but the cancer almost always ends up reappearing in an aggressive form, reducing patients' life expectancy.Approval for the combination of pembrolizumab with enfortumab vedotin was obtained under Health Canada's priority review process. This was based on the KEYNOTE-A39 study, a Phase III, multicentre, randomized, active-controlled clinical trial conducted in partnership by the two laboratories, published in the Annals of Oncology. The cohort comprised 886 previously untreated patients with locally advanced or metastatic urothelial cancer. They were randomized to receive either enfortumab vedotin in combination with pembrolizumab or cisplatin- or carboplatin-based chemotherapy.Results showed a 53% reduction in the risk of death with the combination of enfortumab vedotin and pembrolizumab (hazard ratio: 0.47; 95% confidence interval [CI]: 0.38 to 0.58) compared with chemotherapy. Median overall survival was 31.5 months (95% CI: 25.4 to NA) for the combination of enfortumab vedotin and pembrolizumab, compared with 16.1 months (95% CI: 13.9 to 18.3) for chemotherapy. The researchers also observed a statistically significant improvement in progression-free survival and objective response rate in patients who received pembrolizumab in combination with enfortumab vedotin, compared with the control group. The most frequent adverse events (reported in at least 10% of patients) were fatigue, pruritus, decreased appetite and hypothyroidism.“Metastatic urothelial cancer is an aggressive disease with limited treatment options and a poor prognosis,” said Dr. Normand Blais, hematologist and medical oncologist at the Centre hospitalier de l'Université de Montréal. “This approval represents an important milestone in the treatment of advanced bladder cancer, as this combination is the first and only combination of antibody-drug conjugate and immunotherapy approved in Canada for the treatment of advanced urothelial cancer,” added the physician, quoted in Pfizer’s press release.

Combination of pembrolizumab and enfortumab vedotin approved for the treatment of bladder cancer

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