The Food and Drug Administration has granted regular approval to pembrolizumab (Keytruda) for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Accelerated approval was granted for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
Approval of pembrolizumab for the second-line indication was based on an improvement in overall survival and objective response rate (ORR) in the KEYNOTE-045 trial. Median overall survival was 10.3 months for patients randomized to receive pembrolizumab (n = 270) every 3 weeks, compared with 7.4 months for patients randomized to receive the investigator’s choice of a chemotherapy regimen (paclitaxel [n = 84], docetaxel [n = 84], or vinflunine [n = 87]) every 3 weeks (hazard ratio, 0.73; 95% confidence interval: 0.59-0.91, P =.004). ORR was 21% for pembrolizumab and 11% for chemotherapy (P = .002). All patients had locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy. No statistically significant difference in progression-free survival between the two arms was observed, the FDA said in a statement.
The accelerated approval for the first-line indication was based on an ORR of 28.6% (95% CI, 24-34) in KEYNOTE-052, a single-arm, open-label trial in 370 patients with locally advanced or metastatic urothelial carcinoma who were deemed not eligible for cisplatin-containing chemotherapy. The median response duration was not reached (range, 1.4+-17.8+ months).
The most common adverse reactions reported for those receiving pembrolizumab in either of the two trials included fatigue, musculoskeletal pain, pruritus, decreased appetite, nausea, diarrhea, constipation, and rash. Discontinuation of pembrolizumab occurred in 8% of patients in KEYNOTE-045 and in 11% in KEYNOTE-052. Serious adverse reactions occurred in approximately 40% of pembrolizumab-treated patients, the FDA said.
The recommended pembrolizumab dose and schedule for the treatment of urothelial carcinoma is 200 mg as an intravenous infusion over 30 minutes every 3 weeks. Full prescribing information is available the FDA website.