Top KOLs Discussing PEARLS/KEYNOTE-091
PEARLS/KEYNOTE-091 Key Slides & Visuals
ESMO 2026 slides
| ITT: pembro (n=590) | ITT: placebo (n=587) | Received adjuvant chemo: pembro (n=506) | Received adjuvant chemo: placebo (n=504) | |
|---|---|---|---|---|
| Patients with a DFS event | 56.8% | 61.2% | 56.5% | 62.3% |
| Median DFS, months (95% CI) | 58.7 (47.0–70.4) | 43.3 (35.0–55.6) | 58.7 (47.0–70.5) | 39.1 (31.3–51.7) |
| 6-year DFS, % (95% CI) | 44.0 (39.7–48.2) | 39.2 (35.0–43.2) | 43.6 (38.9–48.1) | 38.1 (33.7–42.5) |
| HR (95% CI) | 0.85 (0.73–0.98) | 0.80 (0.68–0.94) | ||
| PD-L1 TPS ≥50% population (slide footnote) | HR 0.87 (0.65–1.17) |
| ITT: pembro (n=590) | ITT: placebo (n=587) | Received adjuvant chemo: pembro (n=506) | Received adjuvant chemo: placebo (n=504) | |
|---|---|---|---|---|
| Patients who died | 37.1% | 37.3% | 36.4% | 38.1% |
| Median OS, months (95% CI) | NR (100.5–NR) | NR (110.4–NR) | NR (100.5–NR) | NR (103.6–NR) |
| 6-year OS, % (95% CI) | 68.5 (64.5–72.1) | 66.4 (62.4–70.1) | 68.9 (64.6–72.8) | 65.4 (61.0–69.4) |
| HR (95% CI) | 0.98 (0.81–1.18), one-sided P = 0.41826 | 0.91 (0.74–1.12) |
| ITT: pembro (n=590) | ITT: placebo (n=587) | Received adjuvant chemo: pembro (n=506) | Received adjuvant chemo: placebo (n=504) | |
|---|---|---|---|---|
| Patients with an event | 19.5% | 23.0% | 18.6% | 24.8% |
| Median, months | NR | NR | NR | NR |
| 6-year rate, % (95% CI) | 81.3 (77.7–84.4) | 76.9 (73.1–80.2) | 81.6 (77.7–84.9) | 75.0 (70.8–78.7) |
| HR (95% CI) | 0.81 (0.63–1.03) | 0.69 (0.53–0.91) |
| Cause | Pembro | Placebo |
|---|---|---|
| Cardiovascular disease | 12 (2.0), includes 1 death also associated with COVID-19 | 3 (0.5) |
| COVID-19 | 8 (1.4) | 1 (0.2) |
| Other malignancy | 9 (1.5) | 13 (2.2) |
| Treatment-related adverse events | 4 (0.7) | 0 |
| Other (other causes, other chronic disease, unknown) | 71 (12.1) | 67 (11.4) |
The same four slides were also posted by @HHorinouchi.
Physician reactions to PEARLS/KEYNOTE-091
#ESMO26 Dr. Mary O'Brien presents final analysis of phase III PEARLS/KEYNOTE-091 trial: adjuvant pembrolizumab for resected NSCLC with 87m f/u. In pts who received adjuvant chemo, DFS 58.7 vs 39.1m (HR 0.80) and no difference in survival: OS HR 0.91 with 6y DFS 69% vs 65%. In that group, improved lung cancer specific survival (HR 0.69, 6y rate 82% vs 75%). #ESMOAmbassadors
Context: on the final-analysis slides, in patients who received adjuvant chemotherapy, 6-year OS was 68.9% vs 65.4% and 6-year DFS was 43.6% vs 38.1%.
🆙#ESMO26 Proffered Paper: #LCSM Non-Mets 🔥PEARLS/KEYNOTE-091: Final Analysis of Adjuvant Pembrolizumab (Pembro) in Resected Early-Stage Non–Small-Cell Lung Cancer (NSCLC): Phase 3 Study 🎙️ @drMaryOBr 🔢2511O 🎯Consistent DFS Benefit (HR 0.85, 58.7 vs 43.3mo; n=1177) 🎯6-Yr OS 68.5% vs 66.4% (HR 0.98, NS) 🎯Favorable LCSS Trend (HR 0.81) ☑️NCT02504372 🔗 https://t.co/grEfaUchKN @OncoAlert @Larvol @myESMO @IASLC
PEARLS/KEYNOTE-091 Trial Design
PEARLS/KEYNOTE-091 asked whether 1 year of pembrolizumab after complete resection, and after adjuvant chemotherapy when recommended, prolongs disease-free survival in early-stage NSCLC regardless of PD-L1 expression. Merck Sharp & Dohme sponsored and funded the trial; the EORTC Lung Cancer Group and the European Thoracic Oncology Platform (ETOP) are the legal entities responsible for the study and ran it as EORTC-1416-LCG / ETOP 8-15. Patients were recruited from 196 centers in 29 countries between January 2016 and May 2020. The final analysis was presented by Mary O’Brien, MD, at ESMO 2026 (abstract 2511O, Proffered paper: Non-metastatic NSCLC and other thoracic malignancies, October 26, 2026), with Jordi Remon Masip, MD, as invited discussant.
Study Design
Randomized 1:1, triple-blind, placebo-controlled phase 3 (NCT02504372); 590 vs 587 patients. Stratified by stage (IB vs II vs IIIA), PD-L1 TPS (<1% vs 1–49% vs ≥50%), receipt of adjuvant chemotherapy and geographic region.
Population
Completely resected (R0) stage IB (T ≥4 cm), II or IIIA NSCLC per AJCC v7, any histology and PD-L1 level (central testing with PD-L1 IHC 22C3 pharmDx), ECOG PS 0–1, no evidence of disease. Adjuvant chemotherapy (≤4 cycles) considered for IB, strongly recommended for II–IIIA; 86% received it.
Interventions
Pembrolizumab 200 mg IV or placebo every 3 weeks for up to 18 administrations (about 1 year).
Endpoints
Dual primary: investigator-assessed DFS in the ITT and PD-L1 TPS ≥50% populations. Secondary: DFS in TPS ≥1%; OS in ITT, TPS ≥50% and TPS ≥1%; lung cancer–specific survival in ITT; safety. Exploratory: health-related quality of life.
Presenter & Discussant
Presenter: Mary E. O’Brien, MD (Royal Marsden Hospital, London), first author of the 2022 Lancet Oncology report. Invited discussant: Jordi Remon Masip, MD.
Data Cuts
Second interim analysis: data cutoff September 20, 2021 (median follow-up 35.6 months). Final analysis: data cutoff January 21, 2026 (median follow-up 87.7 months).
PEARLS/KEYNOTE-091 in the News
PEARLS/KEYNOTE-091 Questions
What is the PEARLS/KEYNOTE-091 trial?
PEARLS/KEYNOTE-091 (NCT02504372; EORTC-1416-LCG) is a randomized, triple-blind, placebo-controlled phase 3 trial sponsored by Merck (MSD) and run with the EORTC Lung Cancer Group and ETOP. It enrolled 1,177 patients with completely resected stage IB (tumor ≥4 cm), II or IIIA NSCLC (AJCC 7th edition), of any PD-L1 level, who were randomized to pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses (about 1 year). Adjuvant chemotherapy (up to 4 cycles) was considered for stage IB and strongly recommended for stage II–IIIA; 1,010 patients (86%) received it.
What did the final analysis show at ESMO 2026?
At the final analysis (abstract 2511O, data cutoff January 21, 2026; median follow-up 87.7 months), median DFS was 58.7 vs 43.3 months in the ITT population (HR 0.85, 95% CI 0.73–0.98) and 58.7 vs 39.1 months in patients who received adjuvant chemotherapy (HR 0.80, 0.68–0.94). Overall survival did not differ: HR 0.98 (0.81–1.18), one-sided P = 0.41826, with 6-year OS of 68.5% vs 66.4%.
Did adjuvant pembrolizumab improve overall survival?
No statistically significant OS improvement was shown. OS was a secondary endpoint, and the authors note the study was not powered to detect an OS benefit. In patients who received adjuvant chemotherapy, the OS HR was 0.91 (0.74–1.12). Among patients with disease progression, 12.8% in the pembrolizumab arm and 29.3% in the comparator arm received subsequent immunotherapy (2511O slide).
Was the PD-L1 TPS ≥50% primary endpoint met?
No. At the second interim analysis (data cutoff September 20, 2021) the DFS HR in the PD-L1 TPS ≥50% population was 0.82 (95% CI 0.57–1.18; P = 0.14), and at the final analysis it was 0.87 (0.65–1.17). The ITT DFS primary endpoint was met at the second interim analysis (HR 0.76, 0.63–0.91; P = 0.0014; Lancet Oncology 2022).
Is adjuvant pembrolizumab approved?
Yes, after platinum-based chemotherapy. The FDA approved pembrolizumab (KEYTRUDA, Merck) on January 26, 2023 as a single agent for adjuvant treatment following resection and platinum-based chemotherapy for adults with stage IB (T2a ≥4 cm), II or IIIA NSCLC. In the EU, KEYTRUDA monotherapy is indicated for adjuvant treatment of adults with NSCLC at high risk of recurrence following complete resection and platinum-based chemotherapy. Patients who did not receive adjuvant chemotherapy are outside both labels; in that exploratory subgroup (167 patients) the FDA reported a DFS HR of 1.25 (0.76–2.05).
What was the safety profile?
In the final-analysis abstract, grade ≥3 adverse events occurred in 197 of 580 patients (34.0%) with pembrolizumab and 149 of 581 (25.6%) with placebo; grade ≥3 immune-mediated adverse events and infusion reactions occurred in 46 (7.9%) and 11 (1.9%) patients, respectively. Treatment-related adverse events were the cause of 4 deaths (0.7%) in the pembrolizumab arm and none with placebo (2511O slide).