CheckMate 066 trial

Background

Phase III RCT of 418 treatment-naïve patients with unresectable stage III/IV BRAF wild-type melanoma. 5-year follow-up update of CheckMate 066, which established first-line nivolumab over dacarbazine.

Interventions and follow up

Arm A: nivolumab 3mg/kg q2wk
Arm B: dacarbazine 1000mg/m2 q3wk
Primary endpoint: OS
Median follow up: 32.0mo

Results

mOS: 37.5mo vs 11.2mo (nivo vs dacarbazine); HR 0.46, 95%CI 0.36-0.59
5-yr OS: 39% vs 17%
mPFS: 5.1mo vs 2.2mo; HR 0.43, 95%CI 0.34-0.54
5-yr PFS: 28% vs 3%
Normal LDH 5-yr OS / PFS: 48% vs 24% / 32% vs 4%
Elevated LDH 5-yr OS / PFS: 27% vs 7% / 21% vs 0%
ORR: 42% vs 14%

Adverse events

Grade 3-4 treatment-related AEs: 15% (nivolumab) vs 18% (dacarbazine)
Common (any grade, nivolumab): fatigue, pruritus, nausea, diarrhea
Immune-related: hepatitis, colitis, pneumonitis, endocrinopathies; uncommon but management required

Conclusions

First-line nivolumab provided durable, sustained OS and PFS benefit over dacarbazine in BRAF wild-type advanced melanoma, with roughly half of deaths and the majority of progression events averted.

Key Limitations

Restricted to BRAF wild-type disease; dacarbazine is a now-outdated comparator; open-label OS reporting and crossover/subsequent immunotherapy in the control arm may attenuate the apparent benefit.

Clinical Context

Nivolumab is FDA- and EMA-approved for unresectable/metastatic melanoma. CheckMate 066 helped establish anti-PD-1 monotherapy as a standard first-line option, supported by ASCO and ESMO guidelines.

References

Robert C et al, JCO, 2020; PMID:32997575
Robert C et al, NEJM, 2015; PMID:25399552 (primary report)