KEYNOTE Trial Data Presented at ESMO 2025 Congress Reiterate Pembrolizumab’s Benefits in NSCLC

Research presented at the 2025 European Society of Medical Oncology congress highlighted the sustained survival benefits of pembrolizumab (Keytruda, Merck) in certain patients with non–small cell lung cancer (NSCLC).¹

The exploratory 5-year analysis of KEYNOTE-671 (NCT03425643) supported its use as part of a neoadjuvant followed by adjuvant (perioperative) treatment regimen for patients with resectable NSCLC; the 8-year analyses of KEYNOTE-024 (NCT02142738) and KEYNOTE-042 (NCT02220894); and the 10-year analyses of KEYNOTE-001 (NCT01295827) and KEYNOTE-010 (NCT01905657) evaluating pembrolizumab as monotherapy in certain patients with locally advanced or metastatic NSCLC.^1-6

“These long-term data mark a milestone for patients and their families and build upon the transformative progress we’ve already made in NSCLC,” said Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “Across the spectrum of earlier to advanced stages of disease, these results support the long-term survival benefit of [pembrolizumab] in certain patients with NSCLC. We look forward to continued advancements and possibilities for [pembrolizumab] in cancer treatment."¹

What Is The 5-year Follow-up Data from KEYNOTE-671?

For this exploratory 5-year follow-up data from the phase 3 KEYNOTE-671 trial, pembrolizumab in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment following surgery continued to show clinically meaningful improvements in overall survival (OS) and event-free survival (EFS) outcomes in certain patients with resectable stage II, IIIA or IIIB NSCLC, compared with neoadjuvant placebo plus chemotherapy followed by adjuvant placebo alone.

After a median follow-up of about 60.4 months (range: 42.6–85.8), the 5-year OS rates were 64.6% (95% CI, 59.5%–69.2%) and 53.6% (95% CI, 48.3%–58.6%) for the pembrolizumab regimen and chemotherapy-placebo regimen, respectively. Median OS was not reached (NR; 95% CI, NR–NR) for patients who received the KEYTRUDA regimen compared with 70.7 months (95% CI, 53.7–NR) for those who received the chemotherapy-placebo regimen.^1,2

The 5-year EFS rate was approximately 49.9% (95% CI, 44.6%–55.0%) for the pembrolizumab regimen compared with 26.5% (95% CI, 21.7%–31.5%) for the chemotherapy-placebo regimen. Median EFS was 57.1 months (95% CI, 38.0–NR) for patients who received the pembrolizumab regimen compared with 18.4 months (95% CI, 14.8–22.1) for patients who received the chemotherapy-placebo regimen. The pembrolizumab regimen reduced the risk of death by about 28% (HR = 0.72 [95% CI, 0.56-0.93]; p = .0103) compared to the chemotherapy-placebo regimen.^1,2

Additionally, grade 3 or higher treatment-related adverse events (TRAEs) occurred in 45.2% of patients receiving the pembrolizumab regimen and 37.8% of patients receiving the chemotherapy-placebo regimen.^1,2

What Did the Data Say in the KEYNOTE-024 and KEYNOTE-042 Studies?

Both KEYNOTE-024 and KEYNOTE-042, which evaluated pembrolizumab as a monotherapy in certain patients with locally advanced or metastatic NSCLC, demonstrated that pembrolizumab had a superior median OS. In KEYNOTE-024, the respective median OS were 26.3 months (95% CI,18.3–40.4) and 13.4 months (95% CI, 9.4–18.3) for pembrolizumab and chemotherapy (HR = 0.65 [95% CI, 0.50–0.83]) in patients with a tumor proportion score (TPS) of 50% or higher.

In KEYNOTE-042, the median OS for patients receiving pembrolizumab with a TPS of 1% or greater was 16.4 months (95% CI, 14.0–19.6) compared with 12.1 months (95% CI, 11.3–13.3) for chemotherapy (HR = 0.78 [95% CI, 0.69–0.88]), and for patients with a TPS of 50% or greater, the medians were 20.0 months (95% CI, 15.9–24.2) versus 12.2 months (95% CI, 10.4–14.6), respectively (HR = 0.70 [95% CI, 0.59–0.83]).^1,3,4

According to the manufacturer’s news release, prior research indicated that pembrolizumab reduced the risk of disease progression or death by 50% (HR = 0.50 [95% CI, 0.37–0.68]; p < .001) in KEYNOTE-024 and by 31% (HR = 0.69 [95% CI, 0.56–0.85]; p = .0006) in patients with a TPS of 50% or greater and by 19% (HR = 0.81 [95% CI, 0.71–0.93]; p = .0036) in patients with a TPS of 1% or greater in KEYNOTE-042.^1,3,4

What Were the Results of the KEYNOTE-001 and KEYNOTE-010 Trials?

As in the KEYNOTE-024 and KEYNOTE-042 trials, pembrolizumab also improved median OS in patients with NSCLC. In KEYNOTE-001, the median OS rates were about 13.2 months (95% CI, 10.5–15.3) and 17.3 months (95%CI, 13.7–24.8) in those with any TPS score and a TPS of 50% or greater.^1,5 It is important to note that KEYNOTE-001 did not compare pembrolizumab with other agents or therapies.¹

In KEYNOTE-010, the median OS for patients receiving pembrolizumab with a TPS of 1% or greater was about 11.8 months (95% CI, 10.3–13.0) compared with 8.3 months (95% CI, 7.5–9.5) for chemotherapy (HR = 0.66 [95% CI, 0.58–0.76]). For patients with a TPS of 50% or greater, these median OS rates were 16.6 months (95% CI, 12.1–21.2) and 8.2 months (95% CI, 6.4–9.8) for pembrolizumab and chemotherapy, respectively (HR = 0.55 [95% CI, 0.44–0.68]).^1,6

In the KEYNOTE-001 primary analysis, pembrolizumab achieved an objective response rate of 41% in patients with a TPS of 50% or greater, with all responses being partial (95% CI, 29–54). Among responders, 84% maintained their response, including 11 patients with ongoing responses lasting six months or longer. Additionally, in KEYNOTE-010, pembrolizumab significantly improved outcomes compared with chemotherapy in patients with a TPS of 1% or greater and 50% or greater. In those with TPS of 1% or greater, the risk of death was reduced by 29% (HR = 0.71 [95% CI, 0.58–0.88]; p < .001) and 39% (HR = 0.61 [95% CI, 0.49–0.75]; p < .001), respectively, and the risk of disease progression or death by 12% (HR = 0.88 [95% CI, 0.73–1.04]; p = .068) and 21% (HR = 0.79 [95% CI, 0.66–0.94]; p = .005). For TPS 50% or greater, reductions in risk of death were 46% (HR = 0.54 [95% CI, 0.38–0.77]; p < .001) and 50% (HR = 0.50 [95% CI, 0.36–0.70]; p < .001), and the risk of disease progression or death was 42% (HR = 0.58 [95% CI, 0.43–0.77]; p < .001) and 41% (HR = 0.59 [95% CI, 0.45–0.78]; p < .001).^1,5,6

“Historically, patients with advanced NSCLC faced a poor prognosis, with long-term survival considered unlikely,” said Edward B. Garon, MD, MS, professor of medicine, principal investigator for KEYNOTE-001, David Geffen School of Medicine, the University of California, Los Angeles, said in the news release. “The long-term results from these 4 trials show that pembrolizumab has helped change what certain patients with advanced NSCLC can hope to achieve.”¹

REFERENCES

1. Merck. KEYTRUDA® (pembrolizumab) Demonstrates Long-Term Survival Benefit in Certain Patients With Earlier or Advanced Stages of Non-Small Cell Lung Cancer (NSCLC). News release. October 20, 2025. Accessed October 28, 2025. https://www.merck.com/news/keytruda-pembrolizumab-demonstrates-long-term-survival-benefit-in-certain-patients-with-earlier-or-advanced-stages-of-non-small-cell-lung-cancer-nsclc/

2. Efficacy and Safety of Pembrolizumab (MK-3475) With Platinum Doublet Chemotherapy as Neoadjuvant/​Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (MK-3475-671/​KEYNOTE-671). ClinicalTrials.gov identifier: NCT03425643. Updated December 3, 2024. Accessed October 28, 2025. https://www.clinicaltrials.gov/study/NCT03425643

3. Study of Pembrolizumab (MK-3475) Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (MK-3475-024/​KEYNOTE-024). ClinicalTrials.gov identifier: NCT02142738. Updated June 13, 2022. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT02142738

4. Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/​KEYNOTE-042). ClinicalTrials.gov identifier: NCT02220894. Updated October 10, 2023. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT02220894

5. Study of Pembrolizumab (MK-3475) in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/​MK-3475-001/​KEYNOTE-001) (KEYNOTE-001). ClinicalTrials.gov identifier: NCT01295827. Updated December 13, 2019. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT01295827

6. Study of Two Doses of Pembrolizumab (MK-3475) Versus Docetaxel in Previously Treated Participants With Non-Small Cell Lung Cancer (MK-3475-010/​KEYNOTE-010). ClinicalTrials.gov identifier: NCT01905657. Updated October 6, 2021. Accessed October 28, 2025. https://clinicaltrials.gov/study/NCT01905657