Major Breakthrough: Five-year Survival In Nsclc Patients Treated With First-line Pembrolizumab

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Medically reviewed by Dr. Shani Saks on Feb. 21, 2025

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Pembrolizumab offered long-term efficacy in patients with non-small cell lung cancer (NSCLC), as shown by a 5-year survival rate of 26.9 months.
Key Findings:
• NSCLC patients treated with pembrolizumab had a 5-year survival of 26.9 months and a median overall survival (OS) of 21.8 months.
• The Eastern Cooperative Oncology Group-performance status (ECOG-PS), age, and programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) predicted survival in pembrolizumab-treated NSCLC patients.
• Survival rate and progression-free survival were similar between the study population and the KEYNOTE-024 (KN024) look-alike cohort.
• The 5-year survival rate was the longest in those who discontinued treatment due to completion.
• Real-world immune-related adverse events (rw-irAEs) affected 43.8% of patients.
Introduction: Real-World Data on Pembrolizumab’s Long-Term Efficacy Is Limited
Pembrolizumab is ...
... a front-line treatment for advanced NSCLC with a PD-L1 TPS of ≥ 50%. However, there is scarce real-world evidence of the long-term efficacy of PD-L1 inhibitor monotherapy in NSCLC patients with a high PD-L1 expression.
To address this knowledge gap, a study published in the Journal for ImmunoTherapy for Cancer assessed the 5-year outcomes of a real-world cohort of patients with advanced NSCLC and PD-L1 TPS ≥ 50% who received first-line pembrolizumab monotherapy.
Methodology: Cohort Study
This study assessed the 5-year outcomes of 1,050 patients from 61 institutions across 14 countries (referred to as Pembro-real 5Y). Individual patient-level data (IPD) were also extracted from the KN024 trial experimental arm to compare the long-term outcomes of the two cohorts. The researchers also created a “KN024 look-alike” cohort by excluding patients with
an Eastern Cooperative Oncology Group-performance status (ECOGPS) status of ≥ 2 to assess the reproducibility of clinical trial results. Conditional inference tree analysis was performed to provide a hierarchical organization of long-term benefit determinants.
Results:
• 5-Year Survival Rate and Median OS Were 26.9 and 21.8 Months, Respectively
At the 5-year landmark, 282 patients were alive, resulting in a 5-year survival rate of 26.9%. The median overall survival (OS) was 21.8 months (95% confidence interval (CI): 19.1–25.7, 805 events), while the real-world progression-free survival (rw-PFS) was 10.4 months (95% CI: 8.5–11.8, 862 events). The overall response rate (ORR) was 49.6% (95% CI: 45.2%–54.2%).
Of 962 evaluable patients, 59 experienced a complete response to treatment (6.1%, 95% CI: 4.6%–7.9%). At the data cut-off, 32 patients (54.2%) were progression-free.
• The Strongest Survival Predictors Were ECOG-PS, Age, and PD-L1 TPS
Conditional inference tree analysis showed that ECOG-PS was the strongest determinant for an increased risk of death (p < 0.001), as those with poor PS only had a 5-year survival rate of 12.7% (95% CI: 7.9%–20.3%).
Among patients with an ECOG-PS 0–1, the second determinant was age (p = 0.024), with those aged < 70 years having a 5-year survival rate of 33.8% (95% CI: 28.1%–40.2%).
Patients with an ECOG-PS 0–1, aged ≥ 70 years, and a PD-L1 tumor proportion score (TPS) between 50% and 89% had a 5-year survival rate of 18.6% (95% CI: 13.1%–25.6%). The 5-year survival rate for patients with a PD-L1 TPS ≥ 90% was 33.7% (95% CI: 22.9%–47.8%) (p = 0.028).
• KN024 Look-Alike Cohort Survival Rate, PFS Similar to Overall Study Population
The 5-year survival rate for the KN024 look-alike cohort, which had 208 alive patients, was 29.3% (95% CI: 25.5%–33.6%). The OS was 27.5 months (95% CI: 22.8–31.3, 523 events), which was similar to the OS reported for the overall study population.
The rw-PFS for the KN024 look-alike cohort was 11.4 months (95% CI: 9.7–13.3, 560 events), which was also similar to the overall study population (log-rank p value 0.12). The ORR was 51.7% (95% CI: 46.4%–57.5%, 343 tumor responses out of 663 evaluable patients).
The KN024 IPD cohort, meanwhile, had an OS of 26.4 months (95% CI: 19.5–41.4, 154 patients and 103 events). The log-rank comparison showed a similar overall survival rate (log-rank p-value 0.19), although the Pembro-real 5Y cohort had numerically lower estimates.
The 5-year survival rate for patients in the KN024 look-alike cohort with nonsquamous histology was 29.7% (95% CI: 25.5%–34.4%), with a median OS of 26.8 months (95% CI: 21.5–31.4). Patients with squamous histology had a 5-year survival rate of 26.5% (95% CI: 17.9%–37.9%) and a median OS of 27.9 months (95% CI: 19.6–36.6).
In the overall cohort, patients with PD-L1 TPS ≥ 90% had a median OS of 25.3 months (95% CI: 19.8–31.0) and a 5-year survival rate of 24.4% (136/558, 95% CI: 20.4%–28.8%). Those with PD-L1 TPS 50–89% had a median OS of 18.0 months (95% CI: 16.7–21.6) and a 5-year survival rate of 28.8% (81/281, 95% CI: 20.4%–28.9%).
In the KN024 look-alike subgroup, the 5-year survival rate for patients with PD-L1 TPS ≥ 90% was 26.9% (94/350, 95% CI: 21.8%–32.9%). For those with TPS 50–89%, the 5-year survival rate was 32.0% (64/200, 95% CI: 24.6–40.8).
• 5-Year Survival Rate Was Longest in Patients Who Discontinued Treatment Due to Completion
The 5-year survival rates were 7.9% (52/659) for those who discontinued treatment due to progressive disease, 39.7% (62/156) for those who discontinued due to toxicity, 75.3% (58/77) for those who discontinued due to treatment completion, 67.9% (72/106) for those who discontinued due to other reasons, and 17.6% (3/17) for those whose reason for discontinuation was unknown (p < 0.0001).
• Real-World Immune-Related Adverse Events Affected 43.8% of Patients
Any-grade rw-irAEs affected 43.8% of 1,031 patients. The incidence of grade 3/4 rw-irAEs during the first 2 years of treatment was 13.2%.
Skin-related rw-irAEs of any grade occurred in 13.8% of the patients. Gastrointestinal rw-irAEs occurred in 11.3% of patients while thyroid rw-irAEs impacted 10.1% of patients. The most frequent grade 3/4 toxicities within the first 2 years were gastrointestinal rw-irAEs (3.9%), liver rw-irAEs (3.5%), and pneumonitis (2.6%.)
Among the 220 patients who had a minimum treatment duration of 24 months, the incidence of rw-irAEs occurring after the first 2 years of treatment was 22.3% for any grade rw-irAEs and 5.5% for grade 3/4 rw-irAEs. The KN024 look-alike cohort had a similar incidence of any grade and grade 3/4 rw-irAEs.
Conclusion: Pembrolizumab Offers Real-World, Long-Term Efficacy
This real-world study substantiated the long-term efficacy of pembrolizumab, a finding that was also observed in the KN024 trial, while emphasizing the broader demographics and other challenges present in real-world practice. The analysis also showed the hierarchical role of baseline clinicopathological factors, with ECOG-PS being the most significant predator of treatment benefit, followed by age and PD-L1 expression.
Source:
Cortellini, A., Brunetti, L., Di Fazio, G. R., Garbo, E., Pinato, D. J., Naidoo, J., Katz, A., Loza, M., Neal, J. W., Genova, C., Gettinger, S., Kim, S. Y., Jayakrishnan, R., Zarif, T. E., Russano, M., Pecci, F., Federico, A. D., Awad, M., Alessi, J. V., . . . Hejleh, T. A. (2025). Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: Results from the Pembro-real 5Y global registry. Journal for Immunotherapy of Cancer, 13(2), e010674. https://doi.org/10.1136/jitc-2024-010674
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