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Bending the Curve Trial by Trial
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KEYNOTE-010

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer

Phase 2/3N = 1,034NCT01905657

Population
Previously treated NSCLC with PD-L1 on at least 1% of tumour cells
Design
Randomised (1:1:1), open-label phase 2/3 study at 202 centres in 24 countries. Pembrolizumab 2 mg per kilogram, pembrolizumab 10 mg per kilogram or docetaxel 75 mg per square metre, each every 3 weeks.
Primary endpoint
OS, PFS
Arms
  • Pembrolizumab 2 mg/kg (experimental, n = 345): Pembrolizumab 2 mg per kilogram every 3 weeks
  • Pembrolizumab 10 mg/kg (experimental, n = 346): Pembrolizumab 10 mg per kilogram every 3 weeks
  • Docetaxel (control, n = 343): Docetaxel 75 mg per square metre every 3 weeks
People
Herbst RS
OSHR 0.71 (95% CI 0.58–0.88)Δ median OS+1.9 monthsOSHR 0.61 (95% CI 0.49–0.75)Δ median OS+4.2 monthsPFSHR 0.88 (95% CI 0.74–1.05)Δ median PFS−0.1 months
Show the numbers
Results reported for KEYNOTE-010
EndpointAnalysisPembrolizumab 2 mg/kg / Pembrolizumab 10 mg/kgDocetaxelEffect
OSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 10.4 monthsmedian 8.5 monthsHR 0.71 (95% CI 0.58–0.88)P=0.0008Pembrolizumab 2 mg/kg vs docetaxel. By 30 September 2015, 521 patients had died. Dual primary endpoints were OS and PFS in the total population and in patients with PD-L1 on at least 50% of tumour cells.
OSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 12.7 monthsmedian 8.5 monthsHR 0.61 (95% CI 0.49–0.75)P<0.0001Pembrolizumab 10 mg/kg vs docetaxel.
PFSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 3.9 monthsmedian 4 monthsHR 0.88 (95% CI 0.74–1.05)P=0.07Pembrolizumab 2 mg/kg vs docetaxel; not significant (threshold p<0.001).
PFSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 4 monthsmedian 4 monthsHR 0.79 (95% CI 0.66–0.94)P=0.004Pembrolizumab 10 mg/kg vs docetaxel; the abstract notes no significant difference for the 2 mg/kg comparison and gives p=0.004 for this one, against a stated significance threshold of p<0.001.
OSPD-L1 on at least 50% of tumour cellsprimaryHerbst 2016median 14.9 monthsmedian 8.2 monthsHR 0.54 (95% CI 0.38–0.77)P=0.0002Pembrolizumab 2 mg/kg vs docetaxel.
OSPD-L1 on at least 50% of tumour cellsprimaryHerbst 2016median 17.3 monthsmedian 8.2 monthsHR 0.50 (95% CI 0.36–0.70)P<0.0001Pembrolizumab 10 mg/kg vs docetaxel. Grade 3-5 treatment-related adverse events: 13% (2 mg/kg), 16% (10 mg/kg) and 35% (docetaxel).
Results reported for KEYNOTE-010
EndpointAnalysisPembrolizumab 2 mg/kg / Pembrolizumab 10 mg/kgDocetaxelEffect
OSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 10.4 monthsmedian 8.5 monthsHR 0.71 (95% CI 0.58–0.88)P=0.0008Pembrolizumab 2 mg/kg vs docetaxel. By 30 September 2015, 521 patients had died. Dual primary endpoints were OS and PFS in the total population and in patients with PD-L1 on at least 50% of tumour cells.
OSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 12.7 monthsmedian 8.5 monthsHR 0.61 (95% CI 0.49–0.75)P<0.0001Pembrolizumab 10 mg/kg vs docetaxel.
PFSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 3.9 monthsmedian 4 monthsHR 0.88 (95% CI 0.74–1.05)P=0.07Pembrolizumab 2 mg/kg vs docetaxel; not significant (threshold p<0.001).
PFSTotal population (PD-L1 on at least 1% of tumour cells)primaryHerbst 2016median 4 monthsmedian 4 monthsHR 0.79 (95% CI 0.66–0.94)P=0.004Pembrolizumab 10 mg/kg vs docetaxel; the abstract notes no significant difference for the 2 mg/kg comparison and gives p=0.004 for this one, against a stated significance threshold of p<0.001.
OSPD-L1 on at least 50% of tumour cellsprimaryHerbst 2016median 14.9 monthsmedian 8.2 monthsHR 0.54 (95% CI 0.38–0.77)P=0.0002Pembrolizumab 2 mg/kg vs docetaxel.
OSPD-L1 on at least 50% of tumour cellsprimaryHerbst 2016median 17.3 monthsmedian 8.2 monthsHR 0.50 (95% CI 0.36–0.70)P<0.0001Pembrolizumab 10 mg/kg vs docetaxel. Grade 3-5 treatment-related adverse events: 13% (2 mg/kg), 16% (10 mg/kg) and 35% (docetaxel).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOSPFSPFSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.710.58–0.88
OS0.610.49–0.75
PFS0.880.74–1.05
PFS0.790.66–0.94
OS0.540.38–0.77
OS0.50.36–0.7
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Pembrolizumab 2 mg/kg (experimental)
  • Docetaxel (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPembrolizumab 2 mg/kgDocetaxel
0100.0%100.0%
762.7%56.5%
1342.0%34.6%
2026.4%19.6%
2617.7%12.0%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Pembrolizumab 10 mg/kg (experimental)
  • Docetaxel (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPembrolizumab 10 mg/kgDocetaxel
0100.0%100.0%
864.6%52.1%
1641.8%27.1%
2427.0%14.1%
3217.4%7.4%
Primary publication: Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-1550. PubMedDOI

Appears in

Sources

  1. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-1550.

    PubMedDOI