# KEYNOTE-716

Source: https://onco.cc/trials/keynote-716/  
OnCo record `keynote-716` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Extended adjuvant immunotherapy to thick node-negative melanomas, a group whose risk of relapse rivals stage III.

## Summary

RFS and distant metastasis-free survival improved (FDA approval December 2021 for stage IIB/IIC). Five-year follow-up (ESMO 2025) reported sustained RFS and DMFS benefit; OS not yet mature. The absolute benefit is smaller than in stage III and the trial reignited debate about over-treatment given that most stage II patients never relapse.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT03553836
- Phase: 3
- Setting: Resected stage IIB or IIC melanoma: adjuvant pembrolizumab 1 year vs placebo
- Sponsor: Merck
- Enrolled: 976
- Result: RFS and DMFS improved; 5-year benefit sustained (ESMO 2025).
- Outcomes: Recurrence-free survival (first interim analysis): Pembrolizumab vs Placebo, HR 0.65; Distant metastasis-free survival at 36 months (final DMFS analysis): Pembrolizumab 84.4% vs Placebo 74.7%, HR 0.59; Recurrence-free survival at 36 months: Pembrolizumab 76.2% vs Placebo 63.4%, HR 0.62; Recurrence-free survival at 48 months: Pembrolizumab 71.3% vs Placebo 58.3%, HR 0.62
- Replication: Consistent with the stage III adjuvant trials (KEYNOTE-054, CheckMate 238) and with CheckMate 76K (nivolumab in stage IIB/C, RFS HR 0.42), so adjuvant PD-1 benefit in stage II is replicated across two agents. OS not yet significant.

## Sources

- ClinicalTrials.gov NCT03553836: https://clinicaltrials.gov/study/NCT03553836
- 5-year follow-up, Annals of Oncology 2025: https://www.annalsofoncology.org/article/S0923-7534(25)03159-X/fulltext

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Stage IIB and IIC melanoma](https://onco.cc/cancers/stage-ii-melanoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/)
- people: [Jason J. Luke](https://onco.cc/people/jason-luke/)
- key papers: [KEYNOTE-716: adjuvant pembrolizumab versus placebo in completely resected stage IIB or IIC melanoma](https://onco.cc/key-papers/paper-keynote-716-lancet-2022/), [Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial](https://onco.cc/key-papers/paper-keynote-716-lancet-oncol-2022-update/)
- ideas: [ctDNA-guided adjuvant therapy in stage II-III melanoma](https://onco.cc/ideas/idea-ctdna-guided-adjuvant-melanoma/)

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