FDA Approves Keytruda as First- and Second-Line Therapy for Bladder Cancer

FDA Approves Keytruda as First- and Second-Line Therapy for Bladder Cancer

The U.S. Food and Drug Administration has approved Merck’s anti-PD1 therapy Keytruda (pembrolizumab) for the treatment of patients with locally advanced or metastatic urothelial carcinoma, or bladder cancer.

Keytruda was granted accelerated approval as first-line therapy for patients who cannot receive standard of care chemotherapy containing Platinol (cisplatin). This approval was based on tumor response and duration of response, and may be dependent on further verification and description of clinical benefit in confirmation trials.

Keytruda was also approved as a second-line treatment for those whose disease progressed during or after platinum-based chemotherapy.

The FDA’s decision to approve Keytruda for these two new therapeutic indications was based on results from the KEYNOTE-052 Phase 2 trial (NCT02335424) and the KEYNOTE-045 Phase 3 trial (NCT02256436).

Keytruda was approved at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

As a monoclonal antibody that blocks the interaction between the PD-1 receptor and its ligands, Keytruda increases the body’s ability to activate immune cells to fight cancer. It has been widely explored as a monotherapy and in combination regimens against several types of cancers.

“Keytruda is now available for use as a first-line treatment option for patients with advanced urothelial bladder cancer who are not eligible for the standard of care, cisplatin-based chemotherapy,” Dean F. Bajorin, MD, study investigator and medical oncologist at Memorial Sloan Kettering Cancer Center, said in a press release.

“With the second-line indication, Keytruda also provides a new option for patients with advanced urothelial bladder cancer – and is the only anti-PD-1 therapy to show an overall survival benefit versus chemotherapy in a Phase 3 study,” Bajorin added.

Supporting the first-line approval, the multicenter study KEYNOTE-052 included 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for Platinol-containing chemotherapy. All participants received Keytruda once every three weeks for up to 24 weeks, unless they presented signs of treatment-related toxicity.

The treatment had an objective response rate (ORR) of 29%, including 7% complete responses and 22% partial responses. The duration of response ranged from 1.4 to 17.8 months. At the time of the analysis, less than half of patients who responded had seen their disease progress again, so researchers were unable to assess the median duration of response.

The second-line approval was based on results from the multicenter, placebo-controlled KEYNOTE-045 study, which included 542 patients with locally advanced or metastatic urothelial carcinoma, whose disease progressed on or after platinum-based chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy.

Patients were randomized to receive either Keytruda every three weeks or investigator’s choice chemotherapy. Chemotherapy regimens included Taxol (paclitaxel), Taxotere (docetaxel), or the investigational drug vinflunine.

Overall, Keytruda treatment demonstrated a superior overall survival (OS) compared to the other treatment regimens, with a 27% reduction in the risk of death. Keytruda treatment resulted in a median OS of 10.3 months, compared to 7.4 months in the chemotherapy arm.

No statistically significant difference in progression-free survival (PFS) was observed between groups, with those receiving Keytruda having a median PFS of 2.1 months, compared to 3.3 months in the chemotherapy arm.

Keytruda was also seen to improve objective response rate compared to chemotherapy regimens. The ORR was 21% in the Keytruda-treated group vs. 11% in the chemotherapy group.

“These two indications mark important additions to the growing list of tumors and treatment settings for which Keytruda is now approved. This FDA approval further demonstrates Merck’s commitment to help improve the lives of patients with many types of advanced cancer,” said Roger M. Perlmutter, MD, president of Merck Research Laboratories.