The European Commission has approved pembrolizumab, the company’s anti-PD-1 therapy, for the treatment of certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer.
Specifically, pembrolizumab is approved for use as monotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy, as well as adults who are not eligible for cisplatin-containing chemotherapy.
This follows news of FDA approval of pembrolizumab for cisplatin-ineligible urothelial carcinoma in May, and safety notifications from the FDA being issued after deaths in a trial of pembrolizumab for multiple myeloma.
The EU approval in patients previously treated with platinum-containing chemotherapy was based on superior overall survival (OS) for pembrolizumab versus investigator-choice chemotherapy (paclitaxel, docetaxel, vinflunine) (HR, 0.73 [95% CI: 0.59, 0.91], p=0.002), as demonstrated in the randomised, phase 3 KEYNOTE-045 trial.
The approval in patients ineligible for cisplatin-containing chemotherapy was based on phase 2 data from the KEYNOTE-052 trial, which demonstrated an overall response rate (ORR) of 29 percent (95% CI, 25-34).
There was no statistically significant difference between pembrolizumab and chemotherapy with respect to PFS.
There were 218 events (81%) observed in the pembrolizumab arm, compared to 219 events (81%) in the chemotherapy arm (HR, 0.98 [95% CI: 0.81, 1.19], p=0.416).
The median PFS was 2.1 months (95% CI: 2.0, 2.2) in the pembrolizumab arm, compared to 3.3 months (95% CI: 2.3, 3.5) in the chemotherapy arm.
The approval allows for the marketing of pembrolizumab in these two new indications in all 28 EU member states plus Iceland, Lichtenstein and Norway at a dose of 200 mg every three weeks until disease progression or unacceptable toxicity.
"This approval of pembrolizumab is important for patients with advanced urothelial carcinoma,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories, who produce pembrolizumab. “Our focus is now on working with health authorities in Europe to ensure access for these patients as quickly as possible.”
“Despite advances, there remain limited treatment options available to patients with locally advanced or metastatic urothelial carcinoma who are either not eligible to receive cisplatin-containing chemotherapy – which is platinum-based and currently the standard of care – or for those patients whose cancer returns after receiving prior platinum-containing chemotherapy,” said professor Ronald de Wit, M.D., Ph.D., group leader experimental systemic therapy of urogenital cancers, Erasmus MC Cancer Institute. “It is exciting that with this approval of pembrolizumab, we now also have a new treatment option for patients previously treated with platinum-containing chemotherapy that has shown a clinically meaningful and improved overall survival benefit versus chemotherapy in this difficult-to-treat population.”