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.
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Cortellini Alessio, Brunetti Leonardo, Di Fazio Giuseppina Rita, Garbo Edoardo, Pinato David J, Naidoo Jarushka, Katz Artur, Loza Monica, Neal Joel W, Genova Carlo, Gettinger Scott, Kim So Yeon, Jayakrishnan Ritujith, El Zarif Talal, Russano Marco, Pecci Federica, Di Federico Alessandro, Awad Mark, Alessi Joao V, Montrone Michele, Owen Dwight Hall, Signorelli Diego, Fidler Mary Jo, Li Mingjia, Camerini Andrea, De Giglio Andrea, Young Lauren, Vincenzi Bruno, Metro Giulio, Passiglia Francesco, Yendamuri Sai, Guida Annalisa, Ghidini Michele, Awosika Nichola O, Napolitano Andrea, Fulgenzi Claudia A M, Grisanti Salvatore, Grossi Francesco, D'Incecco Armida, Josephides Eleni, Van Hemelrijck Mieke, Russo Alessandro, Gelibter Alain, Spinelli Gianpaolo, Verrico Monica, Tomasik Bartłomiej, Giusti Raffaele, Newsom-Davis Thomas, Bria Emilio, Sebastian Martin, Rost Maximilian, Forster Martin, Mukherjee Uma, Landi Lorenza, Mazzoni Francesca, Aujayeb Avinash, Dupont Manuel, Curioni-Fontecedro Alessandra, Chiari Rita, Pantano Francesco, Morabito Alessandro, Leonetti Alessandro, Friedlaender Alex, Addeo Alfredo, Zoratto Federica, De Tursi Michele, Cantini Luca, Roca Elisa, Mountzios Giannis, Della Gravara Luigi, Kalvapudi Sukumar, Inno Alessandro, Bironzo Paolo, Di Marco Barros Rafael, O'Reilly David, Bell Jack, Karapanagiotou Eleni, Monnet Isabelle, Baena Javier, Macerelli Marianna, Majem Margarita, Agustoni Francesco, Cortinovis Diego Luigi, Tonini Giuseppe, Minuti Gabriele, Bennati Chiara, Mezquita Laura, Gorría Teresa, Servetto Alberto, Beninato Teresa, Lo Russo Giuseppe, Rogado Jacobo, Moliner Laura, Biello Federica, Aboubakar Nana Frank, Dingemans Anne-Marie, Aerts Joachim G J V, Ferrara Roberto, Torri Valter, Hejleh Taher Abu, Takada Kazuki, Naqash Abdul Rafeh, Garassino Marina, Peters Solange, Wakelee Heather, Nassar Amin H, Ricciuti Biagio
Аннотация
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.