FDA Approves Keytruda for Advanced or Metastatic Urothelial Carcinoma

The FDA granted pembrolizumab (Keytruda) regular approval for the treatment of locally advanced or metastatic urothelial carcinoma.

Pembrolizumab is approved for patients whose disease progressed during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The approval was based on data from the multicenter, randomized, active-controlled KEYNOTE-045 trial in patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy, according to a press release.

Patients were randomized to receive either 200 mg of pembrolizumab every 3 weeks or the investigator’s choice of paclitaxel, docetaxel, or vinflunine every 3 weeks.

The results of the study showed that pembrolizumab demonstrated statistically significant improvements in overall survival (OS) and objective response rate (ORR) compared with patients administered chemotherapy.

The median OS was 10.3 months for patients in the pembrolizumab arm and 7.4 months in the chemotherapy arms. The ORR was 21% for pembrolizumab and 11% for chemotherapy.

There were no statistically significant differences in progression-free survival observed between the 2 arms, according to the release.

Additionally, the FDA granted accelerated approval to pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy.

The accelerated approval was based on data from the single-arm, open-label KEYNOTE-052 trial in 370 patients who received 200 mg of pembrolizumab every 3 weeks. The median follow-up was 7.8 months. The median response duration as not reached and the ORR was 28.6%.

In either of the 2 trials, the most common adverse events (AEs) reported in at least 205 patients treated with pembrolizumab was fatigue, musculoskeletal pain, pruritus, decreased appetite, nausea, diarrhea, constipation, and rash. Serious AEs occurred in 40% of patients.

Immune-mediated AEs reported in the trials included pneumonitis, colitis, hepatitis, and endocrinopathies.

Discontinuation of treatment occurred in 8% of patients in the KEYNOTE-045 trial and in 11% in KEYNOTE-052. Pembrolizumab dose interruption occurred in approximately 20% of patients in either trial.