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Bending the Curve Trial by Trial
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PEARLS

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer

Phase 3N = 1,177NCT02504372

Population
Completely resected, pathologically confirmed stage IB (tumours 4 cm or larger), II or IIIA NSCLC (AJCC 7th edition), any histology or PD-L1 level, ECOG performance status 0 or 1
Design
Randomised (1:1), triple-blind phase 3 trial at 196 centres in 29 countries. Pembrolizumab 200 mg or placebo every 3 weeks for up to 18 cycles; adjuvant chemotherapy was to be considered for stage IB and strongly recommended for stage II and IIIA disease. Second interim analysis, data cutoff 20 September 2021.
Primary endpoint
DFS
Arms
  • Pembrolizumab (experimental, n = 590): Pembrolizumab 200 mg every 3 weeks for up to 18 cycles
  • Placebo (control, n = 587): Placebo every 3 weeks for up to 18 cycles
People
O'Brien M, EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 Investigators
DFSHR 0.76 (95% CI 0.63–0.91)Δ median DFS+11.6 monthsDFSHR 0.82 (95% CI 0.57–1.18)
Show the numbers
Results reported for PEARLS
EndpointAnalysisPembrolizumabPlaceboEffect
DFSinterimmedian follow-up 35.6 monthsO'Brien 2022median 53.6 monthsmedian 42 monthsHR 0.76 (95% CI 0.63–0.91)P=0.0014Dual primary endpoint (overall population). The 95% CIs of both medians run to not reached (39.2 and 31.3 months lower bounds), so no ci95 is entered. Grade 3 or worse adverse events: 34% (198 of 580) vs 26% (150 of 581).
DFSPD-L1 TPS 50% or greater (168 pembrolizumab, 165 placebo)interimmedian follow-up 35.6 monthsO'Brien 2022——HR 0.82 (95% CI 0.57–1.18)P=0.14Dual primary endpoint (PD-L1 TPS 50% or greater population). Median DFS not reached in either arm; the difference was not statistically significant.
Results reported for PEARLS
EndpointAnalysisPembrolizumabPlaceboEffect
DFSinterimmedian follow-up 35.6 monthsO'Brien 2022median 53.6 monthsmedian 42 monthsHR 0.76 (95% CI 0.63–0.91)P=0.0014Dual primary endpoint (overall population). The 95% CIs of both medians run to not reached (39.2 and 31.3 months lower bounds), so no ci95 is entered. Grade 3 or worse adverse events: 34% (198 of 580) vs 26% (150 of 581).
DFSPD-L1 TPS 50% or greater (168 pembrolizumab, 165 placebo)interimmedian follow-up 35.6 monthsO'Brien 2022——HR 0.82 (95% CI 0.57–1.18)P=0.14Dual primary endpoint (PD-L1 TPS 50% or greater population). Median DFS not reached in either arm; the difference was not statistically significant.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
DFSDFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
DFS0.760.63–0.91
DFS0.820.57–1.18
Illustrative — modelled from reported values, not trial data. DFS, interim.
0%25%50%75%100%020406080100120Months (modelled)
  • Pembrolizumab (experimental)
  • Placebo (control)

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

Data table (modelled values)
MonthsPembrolizumabPlacebo
0100.0%100.0%
3464.4%57.1%
6742.0%33.1%
10127.1%18.9%
13417.7%11.0%
Primary publication: O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274-1286. PubMedDOI

Appears in

Sources

  1. O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274-1286.

    PubMedDOI