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
Por:
Cortellini, A, Brunetti, L, Di Fazio, GR, Garbo, E, Pinato, DJ, Naidoo, J, Katz, A, Loza, M, Neal, JW, Genova, C, Gettinger, S, Kim, SY, Jayakrishnan, R, El Zarif, T, Russano, M, Pecci, F, Di Federico, A, Awad, M, Alessi, J, Montrone, M, Owen, DH, Signorelli, D, Fidler, MJ, Li, MJ, Camerini, A, De Giglio, A, Young, L, Vincenzi, B, Metro, G, Passiglia, F, Yendamuri, S, Guida, A, Ghidini, M, Awosika, NO, Napolitano, A, Fulgenzi, CAM, 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, Sebastian, M, Rost, M, Forster, M, Mukherjee, U, Landi, L, Mazzoni, F, Aujayeb, A, Dupont, M, Curioni-Fontecedro, A, Chiari, R, Pantano, F, Morabito, A, Leonetti, A, Friedlaender, A, Addeo, A, Zoratto, F, De Tursi, M, Cantini, L, Roca, E, Mountzios, G, Della Gravara, L, Kalvapudi, S, Inno, A, Bironzo, P, Barros, RD, O'Reilly, D, Bell, J, Karapanagiotou, E, Monnet, I, Baena, J, Macerelli, M, Majem, M, Agustoni, F, Cortinovis, DL, Tonini, G, Minuti, G, Bennati, C, Mezquita, L, Gorría, T, Servetto, A, Beninato, T, Lo Russo, G, Rogado, J, Moliner, L, Biello, F, Nana, FA, Dingemans, AM, Aerts, JGJ, Ferrara, R, Torri, V, Abu Hejleh, T, Takada, K, Naqash, AR, Garassino, M, Peters, S, Wakelee, H, Nassar, AH, Ricciuti, B
Publicada:
4 feb 2025
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.
Filiaciones:
Cortellini, A:
Fdn Policlin Univ Campus Biomed, Operat Res Unit Med Oncol, Rome, Italy
Imperial Coll London, Hammersmith Hosp Campus, Dept Surg & Canc, London, England
Univ Campus Biomed Roma, Dept Med & Surg, Rome, Italy
Brunetti, L:
Fdn Policlin Univ Campus Biomed, Operat Res Unit Med Oncol, Rome, Italy
Imperial Coll London, Hammersmith Hosp Campus, Dept Surg & Canc, London, England
Univ Campus Biomed Roma, Dept Med & Surg, Rome, Italy
Di Fazio, GR:
Fdn Policlin Univ Campus Biomed, Operat Res Unit Med Oncol, Rome, Italy
Univ Campus Biomed Roma, Dept Med & Surg, Rome, Italy
Garbo, E:
Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Pinato, DJ:
Imperial Coll London, Hammersmith Hosp Campus, Dept Surg & Canc, London, England
Univ Piemonte Orientale, AOU Maggiore Carita Hosp, Translat Med Dept, Novara, Italy
Naidoo, J:
Beaumont Hosp, Dept Oncol, Beaumont RCSI Canc Ctr, Dublin, Ireland
RCSI Univ Hlth Sci, Dublin, Ireland
Johns Hopkins Univ, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA
Katz, A:
Hosp Sirio Libanes, Oncol Ctr, Sao Paulo, SP, Brazil
Loza, M:
Stanford Univ, Dept Med, Stanford Canc Inst, Div Oncol, Stanford, CA 94305 USA
Neal, JW:
Stanford Univ, Dept Med, Stanford Canc Inst, Div Oncol, Stanford, CA 94305 USA
Genova, C:
IRCCS Osped Policlin San Martino, Acad Oncol Unit, Genoa, Italy
Gettinger, S:
Yale Sch Med, Dept Internal Med, Yale Canc Ctr, Sect Med Oncol, New Haven, CT USA
Kim, SY:
Yale Sch Med, Dept Internal Med, Yale Canc Ctr, Sect Med Oncol, New Haven, CT USA
Jayakrishnan, R:
Yale Sch Med, Dept Internal Med, Yale Canc Ctr, Sect Med Oncol, New Haven, CT USA
El Zarif, T:
Yale Sch Med, Dept Internal Med, Yale Canc Ctr, Sect Med Oncol, New Haven, CT USA
Russano, M:
Fdn Policlin Univ Campus Biomed, Operat Res Unit Med Oncol, Rome, Italy
Pecci, F:
Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Di Federico, A:
Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Awad, M:
Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Alessi, J:
Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Montrone, M:
IRCCS Ist Tumori Giovanni Paolo II, Med Thorac Oncol Unit, Bari, Italy
Owen, DH:
Ohio State Univ, Dept Internal Med, Div Med Oncol, Comprehens Canc Ctr, Columbus, OH 43210 USA
Ohio State Univ, Pletonia Inst Immunooncol, OSUCC James, Columbus, OH 43210 USA
Signorelli, D:
ASST Grande Osped Metropolitano Niguarda, Niguarda Canc Ctr, Milan, Italy
Fidler, MJ:
Rush Univ, Med Ctr, Div Hematol Oncol Stem Cell Transplant, Chicago, IL 60612 USA
Li, MJ:
Ohio State Univ, Dept Internal Med, Div Med Oncol, Comprehens Canc Ctr, Columbus, OH 43210 USA
Camerini, A:
Azienda USL Toscana Nord Ovest, Versilia Hosp, Med Oncol, Lido Di Camaiore, Italy
De Giglio, A:
Univ Bologna, Dept Med & Surg Sci DIMEC, Bologna, Italy
Young, L:
Albert Einstein Coll Med, Montefiore Med Ctr, Dept Oncol, New York, NY USA
Vincenzi, B:
Fdn Policlin Univ Campus Biomed, Operat Res Unit Med Oncol, Rome, Italy
Univ Campus Biomed Roma, Dept Med & Surg, Rome, Italy
Metro, G:
Azienda Osped Perugia, Santa Maria Misericordia Hosp, Med Oncol, Perugia, Italy
Passiglia, F:
Univ Turin, San Luigi Hosp, Dept Oncol, Orbassano, Italy
Yendamuri, S:
Roswell Park Comprehens Canc Ctr, Dept Thorac Surg, Buffalo, NY USA
Guida, A:
Azienda Osped Santa Maria Terni, SC Oncol Med & Traslaz, Terni, Italy
Ghidini, M:
Fdn IRCCS Ca Granda Osped Maggiore Policlin, Med Oncol, Milan, Italy
Awosika, NO:
Imperial Coll London, Hammersmith Hosp Campus, Dept Surg & Canc, London, England
Napolitano, A:
Royal Marsden NHS Fdn Trust, Sarcoma Unit, London, England
Fulgenzi, CAM:
Imperial Coll London, Hammersmith Hosp Campus, Dept Surg & Canc, London, England
Grisanti, S:
Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Brescia, Italy
Grossi, F:
Univ Insubria, Med Oncol Div, Dept Med & Technol Innovat, Varese, Italy
D'Incecco, A:
G Mazzini Hosp Teramo, Teramo, Italy
Josephides, E:
Guys & St Thomas Hosp NHS Trust, Med Oncol, London, England
Van Hemelrijck, M:
Guys & St Thomas Hosp NHS Trust, Med Oncol, London, England
Kings Coll London, Translat Oncol & Urol Res, London, England
Russo, A:
Humanitas Ist Clin Catanese, Med Oncol Dept, Misterbianco, Italy
Gelibter, A:
Sapienza Univ Rome, Dept Clin & Mol Oncol, Rome, Italy
Spinelli, G:
AUSL Latina Aprilia, UOC Territorial Oncol, Aprilia, Italy
Verrico, M:
UOC Oncol A, Policlin Umberto I, Dept Hematol Oncol & Dermatol, Rome, Italy
Tomasik, B:
Med Univ Gdansk, Dept Oncol & Radiotherapy, Gdansk, Poland
Giusti, R:
St Andrea Hosp, Med Oncol, Rome, Italy
Newsom-Davis, T:
Chelsea & Westminster Hosp, Dept Oncol, London, England
Chelsea & Westminster Hosp, Natl Ctr HIV Malignancy, London, England
Bria, E:
Univ Cattolica Sacro Cuore, Fdn Policlin Univ Agostino Gemelli IRCCS, Rome, Italy
Osped Isola Tiberina Gemelli Isola, Rome, Italy
Sebastian, M:
Univ Hosp Frankfurt, Dept Med Hematol Oncol 2, Frankfurt, Germany
Rost, M:
Univ Hosp Frankfurt, Dept Med Hematol Oncol 2, Frankfurt, Germany
Forster, M:
Univ Coll London Hosp NHS Trust, UCL Canc Inst, London, England
Mukherjee, U:
Univ Coll London Hosp NHS Trust, UCL Canc Inst, London, England
Landi, L:
IRCCS Natl Canc Inst Regina Elena, Clin Trials Ctr Phase & Precis Med 1, Rome, Italy
Mazzoni, F:
Careggi Univ Hosp, Med Oncol, Florence, Italy
Aujayeb, A:
Northumbria Healthcare NHS Fdn Trust, Dept Resp Med, North Shields, England
Dupont, M:
Univ Fribourg, Cantonal Hosp Fribourg, Fac Sci & Med, Clin Oncol, Fribourg, Switzerland
Curioni-Fontecedro, A:
Univ Fribourg, Cantonal Hosp Fribourg, Fac Sci & Med, Clin Oncol, Fribourg, Switzerland
Chiari, R:
UOC Oncol, AST Pesaro Urbino, Pesaro, Italy
Pantano, F:
Fdn Policlin Univ Campus Biomed, Operat Res Unit Med Oncol, Rome, Italy
Univ Campus Biomed Roma, Dept Med & Surg, Rome, Italy
Morabito, A:
IRCCS Fdn G Pascale, Thorac Med Oncol, Ist Nazl Tumori, Naples, Italy
Leonetti, A:
Univ Hosp Parma, Med Oncol Unit, Parma, Italy
Friedlaender, A:
Clin Gen Beaulieu, Geneva, Switzerland
Addeo, A:
Univ Hosp Geneva, Oncol Serv, Geneva, Switzerland
Zoratto, F:
Osped Santa Maria Goretti, Latina, Italy
De Tursi, M:
Univ G DAnnunzio, Dept Innovat Technol Med & Dent, Chieti, Italy
Cantini, L:
Fortrea Inc, Durham, NC USA
Roca, E:
Osped P Pederzoli, Oncol Torac Lung Unit, Peschiera Del Garda, Italy
Mountzios, G:
Henry Dunant Hosp Ctr, Dept Med Oncol 4, Athens, Greece
Henry Dunant Hosp Ctr, Clin Trials Unit, Athens, Greece
Della Gravara, L:
AORN Colli Monaldi, Dept Pulm Oncol, Naples, Italy
Kalvapudi, S:
Roswell Park Comprehens Canc Ctr, Dept Thorac Surg, Buffalo, NY USA
Inno, A:
IRCCS Osped Sacro Cuore Don Calabria, Med Oncol Unit, Negrar, Italy
Bironzo, P:
Univ Turin, San Luigi Hosp, Dept Oncol, Orbassano, Italy
Barros, RD:
Guys & St Thomas Hosp NHS Trust, Med Oncol, London, England
O'Reilly, D:
Beaumont Hosp, Dept Oncol, Beaumont RCSI Canc Ctr, Dublin, Ireland
Bell, J:
Beaumont Hosp, Dept Oncol, Beaumont RCSI Canc Ctr, Dublin, Ireland
Karapanagiotou, E:
Guys & St Thomas Hosp NHS Trust, Med Oncol, London, England
Monnet, I:
Ctr Hosp Intercommunal, Serv Pneumol, Creteil, France
Baena, J:
Hosp Univ 12 Octubre, Madrid, Spain
Macerelli, M:
Azienda Sanit Univ Friuli Cent ASUFC, Dept Oncol, Udine, Italy
Majem, M:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Agustoni, F:
Fdn IRCCS Policlin San Matteo, Med Oncol Unit, Pavia, Italy
Cortinovis, DL:
Fdn IRCCS San Gerardo Tintori Monza, Div Med Oncol, Monza, Italy
Univ Milano Bicocca, Dept Clin Med, Monza, Italy
Tonini, G:
Fdn Policlin Univ Campus Biomed, Operat Res Unit Med Oncol, Rome, Italy
Univ Campus Biomed Roma, Dept Med & Surg, Rome, Italy
Minuti, G:
IRCCS Natl Canc Inst Regina Elena, Clin Trials Ctr Phase & Precis Med 1, Rome, Italy
Bennati, C:
AUSL Romagna, Dept Oncohematol, Ravenna, Italy
Mezquita, L:
Hosp Clin Barcelona, Med Oncol Dept, Barcelona, Spain
Gorría, T:
Hosp Clin Barcelona, Med Oncol Dept, Barcelona, Spain
Servetto, A:
Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy
Beninato, T:
Fdn IRCCS Ist Nazl Tumori, Med Oncol Dept, Milan, Italy
Lo Russo, G:
Fdn IRCCS Ist Nazl Tumori, Med Oncol Dept, Milan, Italy
Rogado, J:
Hosp Univ Infanta Lenor, Med Oncol Dept, Madrid, Spain
Moliner, L:
Catalan Inst Oncol, Dept Med Oncol, Lhospitalet De Llobregat, Spain
Biello, F:
Univ Piemonte Orientale, AOU Maggiore Carita Hosp, Translat Med Dept, Novara, Italy
Nana, FA:
Clin Univ St Luc, Div Pneumol, Brussels, Belgium
Dingemans, AM:
Univ Med Ctr, Dept Pulm Med, Erasmus MC Canc Inst, Rotterdam, Netherlands
Aerts, JGJ:
Univ Med Ctr, Dept Pulm Med, Erasmus MC Canc Inst, Rotterdam, Netherlands
Ferrara, R:
Univ Vita Salute San Raffaele, Milan, Italy
IRCCS Osped San Raffaele, Dept Med Oncol, Milan, Italy
Torri, V:
Mario Negri Inst Pharmacol Res IRCCS, Dept Clin Oncol, Milan, Italy
Abu Hejleh, T:
King Hussein Canc Ctr, Dept Internal Med, Med Oncol, Amman, Jordan
Univ Iowa, Dept Internal Med Hematol Oncol & Blood & Marrow, Iowa City, IA USA
Takada, K:
Saiseikai Fukuoka Gen Hosp, Dept Surg, Fukuoka, Japan
Naqash, AR:
Univ Oklahoma, Med Oncol TSET Phase Program 1, Stephenson Canc Ctr, Oklahoma City, OK USA
Garassino, M:
Univ Chicago, Dept Med, Sect Hematol Oncol, Chicago, IL 60637 USA
Peters, S:
Lausanne Univ, Ctr Hosp Univ Vaudois, Lausanne, Switzerland
Wakelee, H:
Stanford Univ, Dept Med, Stanford Canc Inst, Div Oncol, Stanford, CA 94305 USA
Nassar, AH:
Yale Sch Med, Dept Internal Med, Yale Canc Ctr, Sect Med Oncol, New Haven, CT USA
Ricciuti, B:
Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
Green Submitted, gold
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