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

Ricciuti, Biagio;Naqash, Abdul Rafeh;Nassar, Amin H;Wakelee, Heather;Takada, Kazuki;et.al.
(2025) Journal for ImmunoTherapy of Cancer — Vol. 13, n° 2, p. e010674 (2025)

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Authors
  • Ricciuti, Biagioorcid-logo
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  • Naqash, Abdul Rafeh
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  • Nassar, Amin Horcid-logo
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  • Wakelee, Heather
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  • Aboubakar Nana, Frankorcid-logoUCLouvain
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  • Takada, Kazuki
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Abstract
Background Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse. Methods This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y. Individual patient-level data (IPD) from the experimental arm of the KEYNOTE-024 trial were extracted (KN024 IPD cohort) to compare the long-term outcomes between the two cohorts. To further assess the reproducibility of clinical trial results, we reconstructed the “KN024 look-alike” cohort by excluding patients with an Eastern Cooperative Oncology Group-performance status (ECOG-PS)≥2, those requiring corticosteroids with doses ≥10 mg of prednisolone/equivalent, patients with positive/unknown epidermal growth factor receptor/anaplastic lymphoma kinase genotype, and those with pre-existing autoimmune disease. We additionally provided a hierarchical organization of determinants of long-term benefit through a conditional inference tree analysis. Results The study included 1050 patients from 61 institutions across 14 countries, with a median follow-up of 70.3 months. The 5-year survival rate was 26.9% (95% CI: 23.8% to 30.2%), and median OS was 21.8 months (95% CI: 19.1 to 25.7), while 32 (3.0%) patients who achieved a complete response remained progression-free at the data cut-off. The KN024 look-alike cohort had a 5-year survival rate of 29.3% (95% CI: 25.5% to 33.6%) and a median OS of 27.5 months (95% CI: 22.8 to 31.3). Neither the overall study population nor the KN024 look-alike cohort exhibited significantly different OS compared with the KN024 IPD cohort. By the data cut-off, 1015 patients (96.7%) had permanently discontinued treatment: 659 (64.9%) due to progressive disease, 156 (15.4%) due to toxicity, 77 (7.6%) due to treatment completion, and 106 (10.4%) due to other reasons. Overall, 222 participants (21.1%) were treated for a minimum period of 24 months, among them the 5-year survival rates were: 31.7%, 72.7%, 78.6%, 84.2% for patients who discontinued treatment due to progressive disease, toxicity, treatment completion, and other reasons, respectively. Conclusion This study provides valuable real-world evidence that confirms the long-term efficacy of pembrolizumab outside of clinical trials. Hierarchical organization indicates ECOG-PS, age and PD-L1-TPS as the most important predictors of 5-year survival, potentially informing clinical practice.
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Ricciuti, B., Naqash, A. R., Nassar, A. H., Wakelee, H., Peters, S., Garassino, M., 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., et al. (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 (Original work published 2025)