# KEYNOTE-042

Source: https://onco.cc/trials/keynote-042/  
OnCo record `keynote-042` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

KEYNOTE-042 extended pembrolizumab alone to any lung cancer with at least 1 percent PD-L1, but the survival gain came almost entirely from the tumours with 50 percent or more, so chemotherapy is still added for the rest.

## Summary

KEYNOTE-042 randomised 1,274 patients with untreated advanced non-small-cell lung cancer, no EGFR or ALK alteration and a PD-L1 tumour proportion score of at least 1 percent to pembrolizumab alone or to platinum-based chemotherapy. It asked whether the KEYNOTE-024 result in PD-L1-high disease extended down to lower expression.

Overall survival favoured pembrolizumab in every prespecified group: median 20.0 versus 12.2 months in tumours with a score of 50 percent or more (hazard ratio 0.69), and 16.7 versus 12.1 months in the whole population with 1 percent or more (hazard ratio 0.81). In the exploratory group with scores of 1 to 49 percent, however, survival was no different (13.4 versus 12.1 months, hazard ratio 0.92).

The FDA widened the first-line monotherapy label to PD-L1 of 1 percent or more in April 2019, but guidelines reserve monotherapy for scores of 50 percent or more and pair pembrolizumab with chemotherapy below that, following KEYNOTE-189 and KEYNOTE-407.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-17
- Registry id: NCT02220894
- Phase: 3
- Setting: Untreated advanced non-small-cell lung cancer without EGFR or ALK alterations and PD-L1 tumour proportion score of 1 percent or more: pembrolizumab versus platinum doublet chemotherapy
- Sponsor: Merck
- Enrolled: 1274
- Result: Median overall survival 20.0 vs 12.2 months (PD-L1 50% or more, hazard ratio 0.69); 16.7 vs 12.1 months (1% or more, hazard ratio 0.81); no difference at 1 to 49%.
- Outcomes: Overall survival, PD-L1 tumour proportion score 50% or more: Pembrolizumab 20 months vs Platinum chemotherapy 12.2 months, HR 0.69; Overall survival, PD-L1 tumour proportion score 1% or more: Pembrolizumab 16.7 months vs Platinum chemotherapy 12.1 months, HR 0.81
- Replication: Consistent with KEYNOTE-024 in the PD-L1-high group; IMpower110 (atezolizumab) and EMPOWER-Lung 1 (cemiplimab) showed the same pattern of benefit concentrated in high expressers.

## Sources

- ClinicalTrials.gov NCT02220894: https://clinicaltrials.gov/study/NCT02220894
- The Lancet 2019: https://doi.org/10.1016/S0140-6736(18)32409-7

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [PD-L1](https://onco.cc/targets/pdl1/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/)
- terms: [PD-L1 expression testing (22C3, SP142, SP263)](https://onco.cc/terms/pd-l1-testing/), [Tumour proportion score (TPS)](https://onco.cc/terms/tps/)
- people: [Tony S. K. Mok](https://onco.cc/people/tony-mok/)

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