A randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679/ECHO-302)

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dc.article.number1253
dc.catalogadorgjm
dc.contributor.authorLara, Primo N.
dc.contributor.authorVillanueva, Luis
dc.contributor.authorIbáñez Cáceres, Carolina
dc.contributor.authorErman, Mustafa
dc.contributor.authorLee, Jae L.
dc.contributor.authorHeinrich, Daniel
dc.contributor.authorLipatov, Oleg N.
dc.contributor.authorGedye, Craig
dc.contributor.authorGokmen, Erhan
dc.contributor.authorAcevedo, Alejandro
dc.contributor.authorSemenov, Andrey
dc.contributor.authorPark, Se H.
dc.contributor.authorGafanov, Rustem A.
dc.contributor.authorKose, Fatih
dc.contributor.authorJones, Mark
dc.contributor.authorDu, Xiaoqi
dc.contributor.authorMunteanu, Mihaela
dc.contributor.authorPerini, Rodolfo
dc.contributor.authorChoueiri, Toni K.
dc.contributor.authorMotzer, Robert J.
dc.date.accessioned2024-08-01T20:59:12Z
dc.date.available2024-08-01T20:59:12Z
dc.date.issued2024
dc.date.updated2024-07-28T00:04:27Z
dc.description.abstractBackground: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC. Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1. Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2–14.3) and 10.3 months (2.7–13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2–44.1] and sunitinib/pazopanib (29.2% [18.6–41.8]). Grade 3–5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects. Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab.
dc.fechaingreso.objetodigital2024-08-01
dc.format.extent12 páginas
dc.fuente.origenBiomed Central
dc.identifier.citationBMC Cancer. 2024 Jul 25;23(Suppl 1):1253
dc.identifier.urihttps://doi.org/10.1186/s12885-023-10971-7
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87250
dc.information.autorucEscuela de Medicina; Ibáñez Cáceres, Carolina; S/I; 146063
dc.issue.numeroSuppl 1
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaBMC Cancer
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.rights.licenseCC BY 4.0 Attribution 4.0 International Deed
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectRenal cell carcinoma
dc.subjectProgrammed death 1
dc.subjectPD-1
dc.subjectIndoleamine 2,3-deoxygenase 1
dc.subjectIDO1
dc.subjectPembrolizumab
dc.subjectEpacadostat
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleA randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679/ECHO-302)
dc.typeartículo
dc.volumen23
sipa.codpersvinculados146063
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