On October 20, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported new long-term data highlighting the sustained survival benefits of KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in treating non-small cell lung cancer (NSCLC). The results are based on the exploratory five-year analyses of KEYNOTE-671 evaluating KEYTRUDA as part of a neoadjuvant followed by adjuvant (perioperative) treatment regimen for patients with resectable NSCLC; and the eight-year analyses of KEYNOTE-024 and -042 and the 10-year analyses of KEYNOTE-001 and -010 evaluating KEYTRUDA as monotherapy in certain patients with locally advanced or metastatic NSCLC.
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"These long-term data mark a milestone for patients and their families and build upon the transformative progress we’ve already made in non-small cell lung cancer," said Dr. 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 KEYTRUDA in certain patients with NSCLC. We look forward to continued advancements and possibilities for KEYTRUDA in cancer treatment."
In the exploratory five-year follow-up data from the Phase 3 KEYNOTE-671 trial, KEYTRUDA in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after 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 to neoadjuvant placebo plus chemotherapy followed by adjuvant placebo alone. The hazard ratio (HR) for OS for the KEYTRUDA regimen versus the chemotherapy-placebo regimen was 0.74 (95% CI, 0.59-0.92). For EFS, the HR for the KEYTRUDA regimen versus the chemotherapy-placebo regimen was 0.58 (95% CI, 0.48-0.69).
"The five-year benefit demonstrated across overall survival and event-free survival from KEYNOTE-671 supports the continued use of this pembrolizumab-based perioperative regimen as a standard of care for patients with resectable, earlier-stage non-small cell lung cancer," said Dr. Heather Wakelee, principal investigator for KEYNOTE-671, thoracic medical oncologist. "These consistent results are impactful, as they reflect the importance of intervening for certain patients with earlier stages of non-small cell lung cancer." Wakelee is also a professor of medicine at Stanford Medicine.
In the exploratory eight-year analyses from KEYNOTE-024 and KEYNOTE-042 and the exploratory 10-year analyses from KEYNOTE-001 and KEYNOTE-010, KEYTRUDA continued to improve OS in patients with locally advanced or metastatic NSCLC compared to chemotherapy.
In KEYNOTE-001, the median OS for patients receiving KEYTRUDA was 13.2 months (95% CI, 10.5-15.3) in those with any Tumor Proportion Score (TPS) and a median OS of 17.3 months (95% CI,13.7-24.8) in those with a TPS ≥50%. KEYNOTE-001 did not compare KEYTRUDA to another agent or placebo.
In KEYNOTE-010, the median OS for patients receiving KEYTRUDA with a TPS ≥1% was 11.8 months (95% CI, 10.3-13.0) versus 8.3 months (95% CI, 7.5-9.5) for chemotherapy (HR=0.66 [95% CI, 0.58-0.76]). For patients receiving KEYTRUDA, with a TPS ≥50%, the median OS was 16.6 months (95% CI, 12.1-21.2) versus 8.2 months (95% CI, 6.4-9.8) for chemotherapy (HR=0.55 [95% CI, 0.44-0.68]).
In KEYNOTE-024, the median OS for patients receiving KEYTRUDA with a TPS ≥50% was 26.3 months (95% CI,18.3-40.4) versus 13.4 months (95% CI, 9.4-18.3) for chemotherapy (HR=0.65 [95% CI, 0.50-0.83]).
In KEYNOTE-042, the median OS for patients receiving KEYTRUDA with a TPS ≥1% was 16.4 months (95% CI, 14.0-19.6) versus 12.1 months (95% CI, 11.3-13.3) for chemotherapy (HR=0.78 [95% CI, 0.69-0.88]). For patients receiving KEYTRUDA with a TPS ≥50%, the median OS was 20.0 months (95% CI, 15.9-24.2) versus 12.2 months (95% CI, 10.4-14.6) for chemotherapy (HR=0.70 [95% CI, 0.59-0.83]).
Participants from KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042 who achieved a complete response after taking KEYTRUDA and then had progressive disease were eligible for a subsequent anti-cancer therapy including a second course of KEYTRUDA monotherapy.
Additional details about the study designs and results from KEYNOTE-671, KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042, including selected results of previously reported primary analyses, are described below.
"Historically, patients with advanced non-small cell lung cancer 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. "The long-term results from these four trials show that pembrolizumab has helped change what certain patients with advanced NSCLC can hope to achieve."
To date, KEYTRUDA monotherapy or combination regimens have demonstrated sustained survival benefits of five years or more across multiple types of cancer, including certain types of metastatic NSCLC (KEYNOTE-189, KEYNOTE-407), melanoma (KEYNOTE-006, KEYNOTE-054), advanced head and neck (KEYNOTE-048), bladder (KEYNOTE-045) and endometrial (KEYNOTE-775) cancers.
The late-breaking five-year data from KEYNOTE-671 were presented during a mini oral session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2025 (Presentation #LBA67). The eight-year data from KEYNOTE-024 and KEYNOTE-042 and 10-year data from KEYNOTE-001 and KEYNOTE-010 were presented during a poster session at the ESMO (Free ESMO Whitepaper) Congress 2025 (Presentation #3208P).
Study design and additional five-year data from KEYNOTE-671
KEYNOTE-671 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial (ClinicalTrials.gov; NCT03425643) evaluating KEYTRUDA in combination with neoadjuvant chemotherapy, followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent, versus placebo plus neoadjuvant chemotherapy, followed by resection and adjuvant placebo, in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC (per the eighth edition of the American Joint Committee on Cancer [AJCC] Cancer Staging Manual). The trial’s dual primary endpoints are EFS and OS. Key secondary endpoints include pathologic complete response (pCR) and major pathological response (mPR). The study enrolled 797 patients who were randomly assigned (1:1) to receive either:
KEYTRUDA (200 mg intravenously [IV] every three weeks) plus chemotherapy (cisplatin [75 mg/m2 , IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2 , IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4-12 weeks following surgery, KEYTRUDA (200 mg) was administered every three weeks for up to 13 cycles, or;
Placebo (saline IV every three weeks) plus chemotherapy (cisplatin [75 mg/m2 , IV; given on Day 1 of each cycle] and either gemcitabine [1,000 mg/m2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m2, IV; given on Day 1 of each cycle]) for up to four cycles as neoadjuvant therapy prior to surgery. Within 4‑12 weeks following surgery, placebo was administered every three weeks for up to 13 cycles.
After a median follow-up of 60.4 months (range, 42.6-85.8), the five-year OS rate was 64.6% (95% CI, 59.5%-69.2%) for the KEYTRUDA regimen versus 53.6% (95% CI, 48.3%-58.6%) for the chemotherapy-placebo regimen. Median OS was not reached (NR) (95% CI, NR-NR) for patients who received the KEYTRUDA regimen versus 70.7 months (95% CI, 53.7-NR) for patients who received the chemotherapy-placebo regimen.
The five-year EFS rate was 49.9% (95% CI, 44.6%-55.0%) for the KEYTRUDA regimen versus 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 KEYTRUDA regimen versus 18.4 months (95% CI, 14.8-22.1) for patients who received the chemotherapy-placebo regimen.
At the five-year follow-up analysis, Grade ≥3 treatment-related adverse events (TRAEs) occurred in 45.2% of patients receiving the KEYTRUDA regimen and 37.8% of patients receiving the chemotherapy-placebo regimen. Grade ≥3 immune-mediated adverse events (AEs) and infusion reactions occurred in 6.3% of patients receiving the KEYTRUDA regimen and 1.8% of patients receiving the chemotherapy-placebo regimen.
At the study’s previously reported primary analysis, KEYNOTE-671 showed that treatment with the KEYTRUDA regimen reduced the risk of death by 28% (HR=0.72 [95% CI, 0.56-0.93]; p=0.0103) versus the chemotherapy-placebo regimen. For patients who received the KEYTRUDA regimen, median OS was not reached (95% CI, NR-NR) versus 52.4 months (95% CI, 45.7-NR) for patients who received the chemotherapy-placebo regimen. Additionally, the KEYTRUDA regimen reduced the risk of EFS events by 42% (HR=0.58 [95% CI, 0.46-0.72]; p<0.0001) versus the chemotherapy-placebo regimen. For patients who received the KEYTRUDA regimen, median EFS was not reached (95% CI, 34.1-NR) versus 17.0 months (95% CI, 14.3-22.0) for patients who received the chemotherapy-placebo regimen.
(Press release, Merck & Co, OCT 20, 2025, View Source [SID1234656818])
Long-term follow-up data from exploratory analyses of KEYNOTE-001, KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042
In KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042, KEYTRUDA continued to improve OS compared to chemotherapy. In these studies, data showed KEYTRUDA improved OS compared to chemotherapy in patients whose tumors expressed PD-L1 (TPS ≥50%). Overall survival results from these long-term follow-up analyses showed:
KEYTRUDA
Chemotherapy
KEYNOTE-001a,b,c
Any TPS
n/N = 54/550
N/A
10y OS rate (95% CI), %
11.3% (8.5%-14.5%)
N/A
Median OS (95% CI), months
13.2 (10.5-15.3)
N/A
TPS ≥50%
n/N = 25/165
N/A
10y OS rate
19.3% (13.1%-26.5%)
N/A
Median OS (95% CI), months
17.3 (13.7-24.8)
N/A
KEYNOTE-010b,d
TPS ≥1%
n/N = 53/690
n/N = 9/343
10y OS rate
9.3% (7.0%-12.1%)
1.9% (0.7%-4.6%)
Median OS (95% CI), months
11.8 (10.3-13.0)
8.3 (7.5-9.5)
HR (95% CI)
0.66 (0.58–0.76)
TPS ≥50%
n/N = 35/290
n/N = 6/152
10y OS rate
15.5% (11.1%-20.5%)
2.7% (0.7%-7.4%)
Median OS (95% CI), months
16.6 (12.1-21.2)
8.2 (6.4-9.8)
HR (95% CI)
0.55 (0.44-0.68)
KEYNOTE-024a
TPS ≥50%
n/N = 36/154
n/N = 14/151
8y OS rate
24.3% (17.6%-31.5%)
12.8% (7.6%-19.3%)
Median OS (95% CI), months
26.3 (18.3-40.4)
13.4 (9.4-18.3)
HR (95% CI)
0.65 (0.50-0.83)
KEYNOTE-042a
TPS ≥1%
n/N = 66/637
n/N = 27/637
8y OS rate
12.0% (9.5%-14.8%)
4.7% (3.1%-6.9%)
Median OS (95% CI), months
16.4 (14.0-19.6)
12.1 (11.3-13.3)
HR (95% CI)
0.78 (0.69-0.88)
TPS ≥50%
n/N = 41/299
n/N = 13/300
8y OS rate
16.6% (12.5%-21.1%)
6.8% (4.1%-10.5%)
Median OS (95% CI), months
20.0 (15.9-24.2)
12.2 (10.4-14.6)
HR (95% CI)
0.70 (0.59-0.83)
n/N, number of patients in KEYNOTE-587/number of patients in parent study.
afirst-line therapy
bsecond-line+ therapy
cIn KEYNOTE-001, KEYTRUDA was not compared to any other agent or placebo.
dtwo doses of pembrolizumab treatment were combined for these analyses
Limited additional lung cancer-specific deaths occurred since the previously reported five-year data across all four trials.
At the conclusion of these initial studies, participants were eligible to transition to the KEYNOTE-587 extension study for long-term follow-up. The primary endpoint for KEYNOTE-587 is OS. For patients in KEYNOTE-587, the median time from first treatment in KEYNOTE-001 or randomization in KEYNOTE-010, KEYNOTE-024 and KEYNOTE-042 to data cutoff was 124.6 months (range, 118.5-142.2), 115 months (range, 108.8-124.6), 106.4 months (range, 102.4-114.3) and 99 months (range, 86.6-110.2), respectively.
Study design and additional data from KEYNOTE-001
Ten-year outcomes for KEYTRUDA were measured in the Phase 1b KEYNOTE-001 trial (ClinicalTrials.gov; NCT01295827), which evaluated 550 patients with treatment-naïve or previously treated advanced NSCLC. Patients received 2 mg/kg IV of KEYTRUDA every three weeks or 10 mg/kg IV of KEYTRUDA every two weeks or every three weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints included progression-free survival (PFS) and OS.
At the study’s previously reported primary analysis, KEYNOTE-001 showed that KEYTRUDA demonstrated an ORR of 41% in patients with a TPS ≥50%; all responses were partial responses (95% CI, 29-54). Of the patients who responded, 84% continued to respond to treatment with KEYTRUDA, including 11 patients with ongoing responses of six months or longer.
Study design and additional data from KEYNOTE-010
Ten-year outcomes for KEYTRUDA were measured in the Phase 2/3 KEYNOTE-010 trial (ClinicalTrials.gov; NCT01905657), which evaluated patients with metastatic NSCLC whose tumors expressed PD-L1 (TPS ≥1%) that had progressed after platinum-containing chemotherapy and, if appropriate, targeted therapy for EGFR or ALK genomic tumor aberrations. The trial enrolled 1,033 patients who were randomized (1:1:1) to receive 2 mg/kg IV or 10 mg/kg IV of KEYTRUDA every three weeks or chemotherapy (docetaxel) every three weeks. The primary endpoints for this trial were OS and PFS, and secondary endpoints included ORR and duration of response (DOR).
At the study’s previously reported primary analysis, KEYNOTE-010 showed that 2 mg/kg of KEYTRUDA reduced the risk of death by 29% (HR=0.71 [95% CI, 0.58-0.88]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of death by 39% (HR=0.61 [95% CI, 0.49-0.75]; p<0.001) in patients with a TPS ≥1% versus chemotherapy. Two mg/kg of KEYTRUDA reduced the risk of disease progression or death by 12% (HR=0.88 [95% CI, 0.73-1.04]; p=0.068) and 10 mg/kg of KEYTRUDA reduced the risk of disease progression or death by 21% (HR=0.79 [95% CI, 0.66-0.94]; p=0.005) in patients with a TPS ≥1% versus chemotherapy. Additionally, the analysis showed that 2 mg/kg of KEYTRUDA reduced the risk of death by 46% (HR=0.54 [95% CI, 0.38-0.77]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of death by 50% (HR=0.50 [95% CI, 0.36-0.70]; p<0.001) in patients with a TPS ≥50% versus chemotherapy. Two mg/kg of KEYTRUDA reduced the risk of disease progression or death by 42% (HR=0.58 [95% CI, 0.43-0.77]; p<0.001), and 10 mg/kg of KEYTRUDA reduced the risk of disease progression or death by 41% (HR=0.59 [95% CI, 0.45-0.78]; p<0.001) in patients with a TPS ≥50% versus chemotherapy.
Study design and additional data from KEYNOTE-024
Eight-year outcomes for KEYTRUDA were measured in the Phase 3 KEYNOTE-024 trial (ClinicalTrials.gov; NCT02142738), which evaluated patients with previously untreated metastatic NSCLC whose tumors express high levels of PD-L1 (TPS ≥50%) with no EGFR or ALK genomic tumor aberrations. The trial enrolled 305 patients who were randomized (1:1) to receive 200 mg of KEYTRUDA every three weeks or platinum-based chemotherapy. The primary endpoint for this trial was PFS, and secondary endpoints included OS and ORR. In this study, 10.3% (209) of patients transitioned to KEYNOTE-587.
At the study’s previously reported primary analysis, KEYNOTE-024 showed that KEYTRUDA reduced the risk of disease progression or death by 50% (HR=0.50 [95% CI, 0.37-0.68]; p<0.001) versus chemotherapy. Additionally, KEYTRUDA reduced the risk of death by 40% (HR=0.60 [95% CI, 0.41-0.89]; p=0.005) versus chemotherapy.
Study design and additional data from KEYNOTE-042
Eight-year outcomes for KEYTRUDA were measured in the Phase 3 KEYNOTE-042 trial (ClinicalTrials.gov; NCT02220894), which evaluated patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors expressed PD-L1 (TPS ≥1%) and who had not received prior systemic treatment for metastatic NSCLC. The trial enrolled 1,251 patients who were randomized (1:1) to receive 200 mg of KEYTRUDA every three weeks or platinum-based chemotherapy. The primary endpoint for this trial was OS in patients with a TPS ≥50%, ≥20% or ≥1% and secondary endpoints included PFS and ORR as assessed by blinded independent central review (BICR) according to RECIST v1.1 in patients with a TPS ≥50%, ≥20% or ≥1%. In this study, 4.4% (50) of patients transitioned to KEYNOTE-587.
At the study’s previously reported primary analysis, KEYNOTE-042 showed that KEYTRUDA reduced the risk of death by 31% (HR=0.69 [95% CI, 0.56-0.85]; p=0.0006) in patients with a TPS ≥50% and by 19% (HR=0.81 [95% CI, 0.71-0.93]; p=0.0036) in patients with a TPS ≥1% versus chemotherapy. Median OS was 20.0 months (95% CI, 15.4-24.9) for KEYTRUDA in patients with a TPS ≥50% versus 12.2 months (95% CI, 10.4-14.2) for chemotherapy, and 16.7 months (95% CI, 13.9-19.7) for KEYTRUDA in patients with a TPS ≥1% versus 12.1 months (95% CI, 11.3-13.3) for chemotherapy.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. In 2025, the overall five-year survival rate for patients diagnosed with lung cancer was 27% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.