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

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dc.contributor.authorArrieta, Oscar
dc.contributor.authorBarrón-Barrón, Feliciano
dc.contributor.authorRamírez Tirado, Laura Alejandra
dc.contributor.authorZatarain-Barrón, Zyanya Lucia
dc.contributor.authorCardona-Mendoza, Andrés Felipe
dc.contributor.authorDíaz-García, Diego
dc.contributor.authorYamamoto-Ramos, Masao
dc.contributor.authorMota-Vega, Beatriz
dc.contributor.authorCarmona, Amir
dc.contributor.authorPeralta-Alvarez, Marco Polo
dc.contributor.authorBautista, Yolanda
dc.contributor.authorAldaco, Fernando
dc.contributor.authorGerson, Raquel
dc.contributor.authorRolfo, Christian
dc.contributor.authorRosell, Rafael Costa
dc.contributor.orcidCardona-Mendoza, Andrés Felipe [0000-0002-6697-5471]
dc.date.accessioned2020-05-12T00:46:09Z
dc.date.available2020-05-12T00:46:09Z
dc.description.abstractenglishImportance: 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.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jamaoncol.2020.0409?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jamaoncol.2020.0409
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn2374-2497
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlhttps://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/2601
dc.language.isoeng
dc.publisherAmerican Medical Associationspa
dc.publisher.journalJAMA oncologyspa
dc.relation.ispartofseriesJAMA oncology, 2374-2497, 2020spa
dc.relation.urihttps://jamanetwork.com/journals/jamaoncology/article-abstract/2763865?utm_campaign=articlePDF%26utm_medium%3darticlePDFlink%26utm_source%3darticlePDF%26utm_content%3djamaoncol.2020.0409
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2020
dc.rights.localAcceso cerradospa
dc.subject.decsNeoplasias pulmonaresspa
dc.subject.decsInmunoterapiaspa
dc.subject.decsDocetaxelspa
dc.subject.keywordsTargeted and immune cancer therapyspa
dc.subject.keywordsLung cancerspa
dc.subject.keywordsOncologyspa
dc.titleEfficacy 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 trialspa
dc.title.translatedEfficacy 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 trialspa
dc.typearticlespa
dc.type.coarhttps://purl.org/coar/resource_type/c_6501
dc.type.driverinfo:eu-repo/semantics/article
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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Oscar 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
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