FDA approves Keytruda for advanced urothelial carcinoma

The FDA granted accelerated and regular approval to pembrolizumab for the first- and second-line treatments of locally advanced or metastatic urothelial carcinoma, according to the drug’s manufacturer.

Regular approval for the second-line indication included data from the multicenter, randomized, active-controlled KEYNOTE-045 trial, designed to evaluate pembrolizumab (Keytruda, Merck) — an anti–PD-1 monoclonal antibody — in 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.

Patients in that trial received 200 mg pembrolizumab every 3 weeks (n = 270) or investigator’s choice of a chemotherapy regimen — which included paclitaxel, docetaxel or vinflunine — every 3 weeks (n = 272).

Patients in the pembrolizumab arm demonstrated longer median OS (10.3 vs. 7.4 months; HR = 0.73; 95% CI, 0.59-0.91) and a higher objective response rate (21% vs. 11%; P = .002) compared with patients in the chemotherapy arm.

Researchers observed no statistically significant difference in PFS between the arms.

Accelerated approval for the first-line indication included data from the single-arm, open-label KEYNOTE-052 trial, designed to evaluate 200 mg pembrolizumab every 3 weeks in 370 patients with locally advanced or metastatic urothelial carcinoma deemed not eligible for cisplatin-containing chemotherapy (median follow-up, 7.8 months).

Patients demonstrated an ORR of 28.6% (95% CI, 24-34); however, median duration of response had not been reached (range, 1.4+ months to 7.8+ months).

The most common adverse events in both trials included fatigue, musculoskeletal pain, pruritus, decreased appetite, nausea, diarrhea, constipation and rash. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis and endocrinopathies.

Discontinued treatment secondary to adverse reactions occurred in 8% of patients in the KEYNOTE-045 trial and in 11% in the KEYNOTE-052 trial.

Dose interruption occurred in approximately 20% of patients in each trial.

The FDA recommended a dose and schedule of 200 mg pembrolizumab as an IV infusion over 30 minutes every 3 weeks for the treatment of urothelial carcinoma.

Pembrolizumab also is approved for treatment of unresectable or metastatic melanoma; first-line treatment of patients with metastatic non–small cell lung cancer whose tumors have high PD-L1 expression but do not have EGFR or ALK genomic tumor aberrations; patients with metastatic, PD-L1–expressing NSCLC that progressed on or after platinum-containing chemotherapy; and patients with recurrent or metastatic head and neck squamous cell carcinoma that progressed on or after platinum-containing chemotherapy.