| Resumen: |
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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(Hammersmith Hospital Campus)
