Reference: April 2025 | Issue 4 | Vol 11 | Page 41
Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumour proportion score (TPS) ≥50 per cent. However, real-world data on its long-term efficacy remain sparse.
The Pembro-real 5Y study assessed five-year outcomes of first-line pembrolizumab monotherapy in a large, multicentre, real-world cohort of patients with advanced NSCLC and PD-L1 TPS ≥50 per cent. A total of 1,050 patients were recruited from 61 institutions across 14 countries, including Beaumont Hospital, Dublin. Individual patient-level data (IPD) from the experimental arm of the KEYNOTE-024 trial (KN024 IPD cohort) were used to compare long-term outcomes between the two cohorts.
To further assess the reproducibility of clinical trial results, a ‘KN024 look-alike’ cohort was constructed by excluding patients with an Eastern Cooperative Oncology Group-performance status (ECOG-PS) ≥2, those requiring corticosteroids with doses ≥10mg of prednisolone/equivalent, patients with positive/unknown epidermal growth factor receptor/anaplastic lymphoma kinase genotype, and those with pre-existing autoimmune disease. Median follow-up was 70.3 months.
The five-year survival rate was 26.9 per cent (95% CI 23.8%-30.2%), and median overall survival (OS) was 21.8 months (95% CI 19.1-25.7). Thirty-two (3.0%) patients who achieved a complete response remained progression-free at the data cut-off.
The KN024 look-alike cohort had a five-year survival rate of 29.3 per cent (95% CI 25.5%-33.6%) and a median OS of 27.5 months (95% CI 22.8-31.3). 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, 1,015 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, five-year survival rates were 31.7 per cent, 72.7 per cent, 78.6 per cent, and 84.2 per cent for patients who discontinued treatment due to progressive disease, toxicity, treatment completion, and other reasons, respectively.
ECOG-PS emerged as a hierarchical driver of long-term benefit among all variables, followed by age among those with a good PS, and by PD-L1 TPS among patients aged ≥70 years. While ECOG-PS and PD-L1 TPS with the ≥90% cut-off were already known to significantly impact clinical outcomes in this setting, increasing age had not been established as a strong prognostic factor in the context of single-agent PD-1 checkpoint inhibitor treatment in previous literature.
This study, published in February in The Journal for ImmunoTherapy of Cancer, provides valuable real-world evidence that confirms the long-term efficacy of pembrolizumab outside of clinical trials. Moreover, it suggests that ECOG-PS, age, and PD-L1 TPS are the most important predictors of five-year survival.
Reference:
Cortellini A, Brunetti L, Di Fazio GR, Garbo E, Pinato DJ, Naidoo J, et al. Determinants of five-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. J Immunother Cancer. 2025 Feb 4;13(2):e010674. doi: 10.1136/jitc-2024-010674. PMID: 39904562
