Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial

Importance: Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with...

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Autores:
Arrieta, Oscar
Barrón-Barrón, Feliciano
Ramírez Tirado, Laura Alejandra
Zatarain-Barrón, Zyanya Lucia
Cardona-Mendoza, Andrés Felipe
Díaz-García, Diego
Yamamoto-Ramos, Masao
Mota-Vega, Beatriz
Carmona, Amir
Peralta-Alvarez, Marco Polo
Bautista, Yolanda
Aldaco, Fernando
Gerson, Raquel
Rolfo, Christian
Rosell, Rafael Costa
Tipo de recurso:
Article of journal
Fecha de publicación:
2020
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
eng
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/2601
Acceso en línea:
http://hdl.handle.net/20.500.12495/2601
https://jamanetwork.com/journals/jama/fullarticle/10.1001/jamaoncol.2020.0409?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamaoncol.2020.0409
https://repositorio.unbosque.edu.co
Palabra clave:
Neoplasias pulmonares
Inmunoterapia
Docetaxel
Targeted and immune cancer therapy
Lung cancer
Oncology
Rights
openAccess
License
Acceso cerrado
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dc.title.spa.fl_str_mv Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
dc.title.translated.spa.fl_str_mv Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
title Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
spellingShingle Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
Neoplasias pulmonares
Inmunoterapia
Docetaxel
Targeted and immune cancer therapy
Lung cancer
Oncology
title_short Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
title_full Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
title_fullStr Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
title_full_unstemmed Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
title_sort Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trial
dc.creator.fl_str_mv Arrieta, Oscar
Barrón-Barrón, Feliciano
Ramírez Tirado, Laura Alejandra
Zatarain-Barrón, Zyanya Lucia
Cardona-Mendoza, Andrés Felipe
Díaz-García, Diego
Yamamoto-Ramos, Masao
Mota-Vega, Beatriz
Carmona, Amir
Peralta-Alvarez, Marco Polo
Bautista, Yolanda
Aldaco, Fernando
Gerson, Raquel
Rolfo, Christian
Rosell, Rafael Costa
dc.contributor.author.none.fl_str_mv Arrieta, Oscar
Barrón-Barrón, Feliciano
Ramírez Tirado, Laura Alejandra
Zatarain-Barrón, Zyanya Lucia
Cardona-Mendoza, Andrés Felipe
Díaz-García, Diego
Yamamoto-Ramos, Masao
Mota-Vega, Beatriz
Carmona, Amir
Peralta-Alvarez, Marco Polo
Bautista, Yolanda
Aldaco, Fernando
Gerson, Raquel
Rolfo, Christian
Rosell, Rafael Costa
dc.contributor.orcid.none.fl_str_mv Cardona-Mendoza, Andrés Felipe [0000-0002-6697-5471]
dc.subject.decs.spa.fl_str_mv Neoplasias pulmonares
Inmunoterapia
Docetaxel
topic Neoplasias pulmonares
Inmunoterapia
Docetaxel
Targeted and immune cancer therapy
Lung cancer
Oncology
dc.subject.keywords.spa.fl_str_mv Targeted and immune cancer therapy
Lung cancer
Oncology
description Importance: Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy. Objective: To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status. Design, Setting, and Participants: The Pembrolizumab Plus Docetaxel for Advanced Non-Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019. Interventions: The experimental arm received docetaxel on day 1 (75 mg/m2) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy. Main Outcomes and Measures: The primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety. Results: Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P =.01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P =.06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P =.14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P <.001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P <.001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P =.04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P =.03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P =.002). No new safety signals were identified. Conclusions and Relevance: In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations. Trial Registration: ClinicalTrials.gov Identifier: NCT02574598.
publishDate 2020
dc.date.accessioned.none.fl_str_mv 2020-05-12T00:46:09Z
dc.date.available.none.fl_str_mv 2020-05-12T00:46:09Z
dc.type.spa.fl_str_mv article
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identifier_str_mv 2374-2497
instname:Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
url http://hdl.handle.net/20.500.12495/2601
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dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofseries.spa.fl_str_mv JAMA oncology, 2374-2497, 2020
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dc.publisher.spa.fl_str_mv American Medical Association
dc.publisher.journal.spa.fl_str_mv JAMA oncology
institution Universidad El Bosque
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spelling Arrieta, OscarBarrón-Barrón, FelicianoRamírez Tirado, Laura AlejandraZatarain-Barrón, Zyanya LuciaCardona-Mendoza, Andrés FelipeDíaz-García, DiegoYamamoto-Ramos, MasaoMota-Vega, BeatrizCarmona, AmirPeralta-Alvarez, Marco PoloBautista, YolandaAldaco, FernandoGerson, RaquelRolfo, ChristianRosell, Rafael CostaCardona-Mendoza, Andrés Felipe [0000-0002-6697-5471]2020-05-12T00:46:09Z2020-05-12T00:46:09Z2374-2497http://hdl.handle.net/20.500.12495/2601https://jamanetwork.com/journals/jama/fullarticle/10.1001/jamaoncol.2020.0409?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamaoncol.2020.0409instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquehttps://repositorio.unbosque.edu.coapplication/pdfengAmerican Medical AssociationJAMA oncologyJAMA oncology, 2374-2497, 2020https://jamanetwork.com/journals/jamaoncology/article-abstract/2763865?utm_campaign=articlePDF%26utm_medium%3darticlePDFlink%26utm_source%3darticlePDF%26utm_content%3djamaoncol.2020.0409Efficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trialEfficacy and safety of pembrolizumab plus docetaxel vs docetaxel alone in patients with previously treated advanced non-small cell lung cancer: the PROLUNG Phase 2 randomized clinical trialarticleartículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85Neoplasias pulmonaresInmunoterapiaDocetaxelTargeted and immune cancer therapyLung cancerOncologyImportance: Because of socioeconomic factors, many patients with advanced non-small cell lung cancer (NSCLC) do not receive immunotherapy in the first-line setting. It is unknown if the combination of immunotherapy with chemotherapy can provide clinical benefits in immunotherapy-naive patients with disease progression after treatment with platinum-based chemotherapy. Objective: To evaluate the safety and efficacy of the combination of pembrolizumab plus docetaxel in patients with previously treated advanced NSCLC following platinum-based chemotherapy regardless of EGFR variants or programmed cell death ligand 1 status. Design, Setting, and Participants: The Pembrolizumab Plus Docetaxel for Advanced Non-Small Cell Lung Cancer (PROLUNG) trial randomized 78 patients with histologically confirmed advanced NSCLC in a 1:1 ratio to receive either pembrolizumab plus docetaxel or docetaxel alone from December 2016 through May 2019. Interventions: The experimental arm received docetaxel on day 1 (75 mg/m2) plus pembrolizumab on day 8 (200 mg) every 3 weeks for up to 6 cycles followed by pembrolizumab maintenance until progression or unacceptable toxic effects. The control arm received docetaxel monotherapy. Main Outcomes and Measures: The primary end point was overall response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival, and safety. Results: Among 78 recruited patients, 32 (41%) were men, 34 (44%) were never smokers, and 25 (32%) had an EGFR/ALK alteration. Forty patients were allocated to receive pembrolizumab plus docetaxel, and 38 were allocated to receive docetaxel. A statistically significant difference in ORR, assessed by an independent reviewer, was found in patients receiving pembrolizumab plus docetaxel vs patients receiving docetaxel (42.5% vs 15.8%; odds ratio, 3.94; 95% CI, 1.34-11.54; P =.01). Patients without EGFR variations had a considerable difference in ORR of 35.7% vs 12.0% (P =.06), whereas patients with EGFR variations had an ORR of 58.3% vs 23.1% (P =.14). Overall, PFS was longer in patients who received pembrolizumab plus docetaxel (9.5 months; 95% CI, 4.2-not reached) than in patients who received docetaxel (3.9 months; 95% CI, 3.2-5.7) (hazard ratio, 0.24; 95% CI, 0.13-0.46; P <.001). For patients without variations, PFS was 9.5 months (95% CI, 3.9-not reached) vs 4.1 months (95% CI, 3.5-5.3) (P <.001), whereas in patients with EGFR variations, PFS was 6.8 months (95% CI, 6.2-not reached) vs 3.5 months (95% CI, 2.3-6.2) (P =.04). In terms of safety, 23% (9 of 40) vs 5% (2 of 38) of patients experienced grade 1 to 2 pneumonitis in the pembrolizumab plus docetaxel and docetaxel arms, respectively (P =.03), while 28% (11 of 40) vs 3% (1 of 38) experienced any-grade hypothyroidism (P =.002). No new safety signals were identified. Conclusions and Relevance: In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations. Trial Registration: ClinicalTrials.gov Identifier: NCT02574598.Acceso cerradohttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessAcceso abierto2020THUMBNAILOscar Arrieta, MD, MSc; Feliciano Barrón, MD, MSc; Laura Alejandra Ramírez-Tirado, MD, MSc; Zyanya Lucia Zatarain-Barrón, MD, MSc;Andrés F. Cardona, MD, MSc, PhD; Diego Díaz-García, MD; Masao Yamamoto Ramos_2020.pdf.jpgOscar Arrieta, MD, MSc; Feliciano Barrón, MD, MSc; Laura Alejandra Ramírez-Tirado, MD, MSc; Zyanya Lucia Zatarain-Barrón, MD, MSc;Andrés F. Cardona, MD, MSc, PhD; Diego Díaz-García, MD; Masao Yamamoto Ramos_2020.pdf.jpgimage/jpeg5775https://repositorio.unbosque.edu.co/bitstreams/3be310b2-d831-46e2-96c9-6558de89c21a/download7210a811635d1799e7c05fee5d259be7MD53ORIGINALOscar Arrieta, MD, MSc; Feliciano Barrón, MD, MSc; Laura Alejandra Ramírez-Tirado, MD, MSc; Zyanya Lucia Zatarain-Barrón, MD, MSc;Andrés F. Cardona, MD, MSc, PhD; Diego Díaz-García, MD; Masao Yamamoto Ramos_2020.pdfOscar Arrieta, MD, MSc; Feliciano Barrón, MD, MSc; Laura Alejandra Ramírez-Tirado, MD, MSc; Zyanya Lucia Zatarain-Barrón, MD, MSc;Andrés F. Cardona, MD, MSc, PhD; Diego Díaz-García, MD; Masao Yamamoto Ramos_2020.pdfapplication/pdf543611https://repositorio.unbosque.edu.co/bitstreams/50d72e03-0ebf-4889-a208-ce7816d001e7/download922a5ceb8eb7b14abd4a51107916b6e3MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.unbosque.edu.co/bitstreams/e6f056d8-db01-4df4-9d2e-d87994f82890/download8a4605be74aa9ea9d79846c1fba20a33MD52TEXTOscar Arrieta, MD, MSc; Feliciano Barrón, MD, MSc; Laura Alejandra Ramírez-Tirado, MD, MSc; Zyanya Lucia Zatarain-Barrón, MD, MSc;Andrés F. Cardona, MD, MSc, PhD; Diego Díaz-García, MD; Masao Yamamoto Ramos_2020.pdf.txtOscar Arrieta, MD, MSc; Feliciano Barrón, MD, MSc; Laura Alejandra Ramírez-Tirado, MD, MSc; Zyanya Lucia Zatarain-Barrón, MD, MSc;Andrés F. 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