Keynote 052

Background

Single-arm phase II trial of 370 patients with treatment-naive, cisplatin-ineligible, locally advanced or metastatic urothelial carcinoma.

Interventions and follow up

Regimen: Pembrolizumab 200 mg IV q3wk until progression, toxicity, or up to 24 months
Primary endpoint: Objective response rate (ORR) by RECIST v1.1
Median follow up: 56.3 mo

Results

Confirmed ORR: 28.6% (CR 8.9%, PR 19.7%)
Disease control rate: 46.8%
mOS: 11.3 mo
mPFS: 2.2 mo
OS rate: 46.9% at 12 mo; 31.2% at 24 mo

Adverse events

Any-grade treatment-related events: 67.3% of patients
Constitutional/skin: Fatigue 18.1%; pruritus 17.8%; rash 11.6%
Gastrointestinal/endocrine: Decreased appetite 10.8%; diarrhea 9.2%; hypothyroidism 10.0%

Conclusions

First-line pembrolizumab produced durable responses in cisplatin-ineligible advanced urothelial carcinoma, with greatest benefit in high PD-L1 expressers and lymph-node-only disease.

Key Limitations

Single-arm, non-comparative phase II; modest ORR with no randomized survival benefit. Subsequent data and label restrictions limited single-agent first-line immunotherapy to PD-L1-high or platinum-ineligible patients.

Clinical Context

KEYNOTE-052 supported FDA accelerated approval of first-line pembrolizumab for cisplatin-ineligible advanced urothelial carcinoma; the label was later restricted to PD-L1-high or platinum-ineligible patients. With frontline enfortumab vedotin plus pembrolizumab now standard, single-agent first-line immunotherapy is reserved for platinum-unfit patients per ASCO/ESMO.

References

Vuky J et al, JCO, 2020, PMID: 32552471
Balar AV et al (KEYNOTE-052 primary), Lancet Oncol, 2017, PMID: 28967485