Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials

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-y...

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Autores: Cortellini, Alessio|||0000-0002-1209-5735, Brunetti, L., Di Fazio, G.R., Garbo, E., Pinato, David James|||0000-0002-3529-0103, Naidoo, J., Katz, A., Loza, M., Neal, J.W., Genova, C., Gettinger, S., Kim, S.Y.|||0000-0003-4102-5880, Jayakrishnan, R., El Zarif, T., Russano, M., Pecci, F., Di Federico, A.|||0000-0001-8877-4315, Awad, M., Alessi, Joao|||0000-0002-8072-5946, Montrone, M., Owen, D.H., Signorelli, D., Fidler, M.J., Li, Mengyao|||0000-0002-9082-7938, Camerini, A., De Giglio, A., Young, L., Vincenzi, B., Metro, G., Passiglia, F., Yendamuri, S.|||0000-0001-6654-3487, Guida, A., Ghidini, M., Awosika, N.O., Napolitano, A., Fulgenzi, C.A.M., Grisanti, S., Grossi, F., D'incecco, A., Josephides, E., Van Hemelrijck, M., Russo, A., Gelibter, A., Spinelli, G., Verrico, M., Tomasik, B., Giusti, R., Newsom-Davis, T., Bria, E.|||0000-0002-2333-704X, Sebastian, M., Rost, M., Forster, M., Mukherjee, U., Landi, L., Mazzoni, F., Aujayeb, Avinash|||0000-0002-0859-5550, Dupont, M., Curioni-Fontecedro, A., Chiari, R., Pantano, F., Morabito, A.|||0000-0002-1319-9608, Leonetti, A., Friedlaender, A., Addeo, Alfredo|||0000-0003-0988-0828, Zoratto, F., De Tursi, M., Cantini, L., Roca, E., Mountzios, G.|||0000-0002-7780-7836, Della Gravara, L., Kalvapudi, S., Inno, A., Bironzo, P., Di Marco Barros, R., O'reilly, D., Bell, J., Karapanagiotou, E., Monnet, I., Baena, J., Macerelli, M., Majem Tarruella, Margarita|||0000-0002-9919-7485, Agustoni, F., Cortinovis, D.L., Tonini, G., Minuti, G., Bennati, C., Mezquita, Laura|||0000-0003-0936-7338, Gorría, Teresa, Servetto, A., Beninato, T., Lo Russo, G., Rogado, J., Moliner, Laura, Biello, F., Aboubakar Nana, F., Dingemans, A.M., Aerts, J.G.J.V.|||0000-0001-6662-2951, Ferrara, R., Torri, V., Hejleh, T.A., Takada, K., Naqash, A.R., Garassino, M., Peters, S., Wakelee, H., Nassar, A.H.|||0000-0002-4507-2396, Ricciuti, Biagio|||0000-0002-0651-2678
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:320642
Acceso en línea:https://ddd.uab.cat/record/320642
https://dx.doi.org/urn:doi:10.1136/jitc-2024-010674
Access Level:acceso abierto
Palabra clave:Immune Checkpoint Inhibitor
Immunotherapy
Lung Cancer
Descripción
Sumario: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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