KEYNOTE-017

Background

Phase 2, multicenter, open-label, nonrandomized KEYNOTE-017. N=50 advanced (locally advanced or metastatic) Merkel cell carcinoma (MCC), no prior systemic therapy for advanced disease. NEJM 2016 reported initial 26-pt cohort; JCO 2019 update reports full 50-pt cohort. First-line anti-PD-1 (pembrolizumab). ECOG PS 0–1; no PD-L1/MCPyV selection.

Interventions and follow up

Treatment: Pembrolizumab 2 mg/kg IV q3w for up to 2 years (single-arm)
Primary endpoint: ORR (CR+PR) per RECIST 1.1 by independent central review
mFollow up: Median 14.9 months (JCO 2019 update, N=50)

Results

ORR: 56.0% (28/50; 95% CI 41.3–70.0); CR 24% (12), PR 32% (16)
mDOR: Not reached (range 2.7–34.5+ mo); 96% ongoing at 6 mo
mPFS: 16.8 months (95% CI 4.6–NR)
PFS at 24 mo: 48.3%
OS at 24 mo: 68.7%

Adverse events

Grade ≥3 TRAE: 28%
Most common: fatigue, decreased appetite, rash
Immune-mediated: ~24% required systemic steroids or hormone replacement
Treatment-related deaths: None

Conclusions

First-line pembrolizumab achieved 56% ORR with durable responses (mDOR not reached) in advanced MCC, outperforming historical chemotherapy (ORR ~50%, median duration ~3 mo). Established pembrolizumab as a preferred first-line option, with responses durable at 2 years in nearly half of patients.

Key Limitations

Single-arm, nonrandomized; small N (50); rare disease limits power. No comparator arm; efficacy benchmarked against historical chemotherapy. ORR surrogate endpoint; OS immature.

Clinical Context

Supported first-line anti-PD-1 use in advanced MCC; pembrolizumab and avelumab are ASCO/ESMO-endorsed options. Established immunotherapy over chemotherapy as preferred first-line systemic treatment.

References