Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma
BACKGROUND The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage I...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/132151 |
| Acceso en línea: | https://hdl.handle.net/2445/132151 |
| Access Level: | acceso abierto |
| Palabra clave: | Melanoma Placebos Tractament adjuvant del càncer Placebos (Medicine) Adjuvant treatment of cancer |
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Adjuvant Pembrolizumab versus Placebo in Resected Stage III MelanomaEggermont, Alexander MaximiliaanBlank, C.U.Mandala, MarioLong, Georgina V.Atkinson, VictoriaDalle, StéphaneHaydon, AndrewLichinitser, MikhailKhattak, AdnanCarlino, Matteo S.Sandhu, ShahneenLarkin, JamesPuig i Sardà, SusanaAscierto, Paolo AntonioRutkowski, PiotrSchadendorf, DirkKoornstra, RutgerHernandez Aya, LeonelMaio, MicheleEertwegh, Alfonsus J.M. van denGrob, Jean JacquesGutzmer, RalfJamal, RahimaLorigan, PaulIbrahim, NageatteMarreaud, SandrineAkkooi, Alexander Christopher Jonathan vanSuciu, StefanRobert, CarolineMelanomaPlacebosTractament adjuvant del càncerMelanomaPlacebos (Medicine)Adjuvant treatment of cancerBACKGROUND The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. METHODS Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated. RESULTS At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence-free survival than placebo in the overall intention-to-treat population (1-year rate of recurrence-free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9] vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57; 98.4% CI, 0.43 to 0.74; P<0.001) and in the subgroup of 853 patients with PD-L1-positive tumors (1-year rate of recurrence-free survival, 77.1% [95% CI, 72.7 to 80.9] in the pembrolizumab group and 62.6% [95% CI, 57.7 to 67.0] in the placebo group; hazard ratio, 0.54; 95% CI, 0.42 to 0.69; P<0.001). Adverse events of grades 3 to 5 that were related to the trial regimen were reported in 14.7% of the patients in the pembrolizumab group and in 3.4% of patients in the placebo group. There was one treatment-related death due to myositis in the pembrolizumab group. CONCLUSIONS As adjuvant therapy for high-risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrencefree survival than placebo, with no new toxic effects identified. (Massachusetts Medical Society2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/132151Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1056/NEJMoa1802357New England Journal of Medicine, 2018, vol. 378, num. 19, p. 1789-1801https://doi.org/10.1056/NEJMoa1802357(c) Massachusetts Medical Society, 2018info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1321512026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma |
| title |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma |
| spellingShingle |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma Eggermont, Alexander Maximiliaan Melanoma Placebos Tractament adjuvant del càncer Melanoma Placebos (Medicine) Adjuvant treatment of cancer |
| title_short |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma |
| title_full |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma |
| title_fullStr |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma |
| title_full_unstemmed |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma |
| title_sort |
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma |
| dc.creator.none.fl_str_mv |
Eggermont, Alexander Maximiliaan Blank, C.U. Mandala, Mario Long, Georgina V. Atkinson, Victoria Dalle, Stéphane Haydon, Andrew Lichinitser, Mikhail Khattak, Adnan Carlino, Matteo S. Sandhu, Shahneen Larkin, James Puig i Sardà, Susana Ascierto, Paolo Antonio Rutkowski, Piotr Schadendorf, Dirk Koornstra, Rutger Hernandez Aya, Leonel Maio, Michele Eertwegh, Alfonsus J.M. van den Grob, Jean Jacques Gutzmer, Ralf Jamal, Rahima Lorigan, Paul Ibrahim, Nageatte Marreaud, Sandrine Akkooi, Alexander Christopher Jonathan van Suciu, Stefan Robert, Caroline |
| author |
Eggermont, Alexander Maximiliaan |
| author_facet |
Eggermont, Alexander Maximiliaan Blank, C.U. Mandala, Mario Long, Georgina V. Atkinson, Victoria Dalle, Stéphane Haydon, Andrew Lichinitser, Mikhail Khattak, Adnan Carlino, Matteo S. Sandhu, Shahneen Larkin, James Puig i Sardà, Susana Ascierto, Paolo Antonio Rutkowski, Piotr Schadendorf, Dirk Koornstra, Rutger Hernandez Aya, Leonel Maio, Michele Eertwegh, Alfonsus J.M. van den Grob, Jean Jacques Gutzmer, Ralf Jamal, Rahima Lorigan, Paul Ibrahim, Nageatte Marreaud, Sandrine Akkooi, Alexander Christopher Jonathan van Suciu, Stefan Robert, Caroline |
| author_role |
author |
| author2 |
Blank, C.U. Mandala, Mario Long, Georgina V. Atkinson, Victoria Dalle, Stéphane Haydon, Andrew Lichinitser, Mikhail Khattak, Adnan Carlino, Matteo S. Sandhu, Shahneen Larkin, James Puig i Sardà, Susana Ascierto, Paolo Antonio Rutkowski, Piotr Schadendorf, Dirk Koornstra, Rutger Hernandez Aya, Leonel Maio, Michele Eertwegh, Alfonsus J.M. van den Grob, Jean Jacques Gutzmer, Ralf Jamal, Rahima Lorigan, Paul Ibrahim, Nageatte Marreaud, Sandrine Akkooi, Alexander Christopher Jonathan van Suciu, Stefan Robert, Caroline |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Melanoma Placebos Tractament adjuvant del càncer Melanoma Placebos (Medicine) Adjuvant treatment of cancer |
| topic |
Melanoma Placebos Tractament adjuvant del càncer Melanoma Placebos (Medicine) Adjuvant treatment of cancer |
| description |
BACKGROUND The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. METHODS Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated. RESULTS At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence-free survival than placebo in the overall intention-to-treat population (1-year rate of recurrence-free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9] vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57; 98.4% CI, 0.43 to 0.74; P<0.001) and in the subgroup of 853 patients with PD-L1-positive tumors (1-year rate of recurrence-free survival, 77.1% [95% CI, 72.7 to 80.9] in the pembrolizumab group and 62.6% [95% CI, 57.7 to 67.0] in the placebo group; hazard ratio, 0.54; 95% CI, 0.42 to 0.69; P<0.001). Adverse events of grades 3 to 5 that were related to the trial regimen were reported in 14.7% of the patients in the pembrolizumab group and in 3.4% of patients in the placebo group. There was one treatment-related death due to myositis in the pembrolizumab group. CONCLUSIONS As adjuvant therapy for high-risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrencefree survival than placebo, with no new toxic effects identified. ( |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/2445/132151 |
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https://hdl.handle.net/2445/132151 |
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Inglés |
| language_invalid_str_mv |
Inglés |
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Reproducció del document publicat a: https://doi.org/10.1056/NEJMoa1802357 New England Journal of Medicine, 2018, vol. 378, num. 19, p. 1789-1801 https://doi.org/10.1056/NEJMoa1802357 |
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(c) Massachusetts Medical Society, 2018 info:eu-repo/semantics/openAccess |
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(c) Massachusetts Medical Society, 2018 |
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openAccess |
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application/pdf |
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Massachusetts Medical Society |
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Massachusetts Medical Society |
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Articles publicats en revistes (Medicina) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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