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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSantoro, Armando
dc.contributor.authorSu, Wu-Chou
dc.contributor.authorNavarro Mendivil, Alejandro
dc.contributor.authorSimonelli, Matteo
dc.contributor.authorYang, James C. H.
dc.contributor.authorArdizzoni, Andrea
dc.contributor.authorFelip Font, Enriqueta
dc.date.accessioned2022-08-10T06:25:28Z
dc.date.available2022-08-10T06:25:28Z
dc.date.issued2022-04
dc.identifier.citationSantoro A, Su WC, Navarro A, Simonelli M, Yang JCH, Ardizzoni A, et al. Phase Ib/II study of ceritinib in combination with ribociclib in patients with ALK-rearranged non–small cell lung cancer. Lung Cancer. 2022 Apr;166:170–7.
dc.identifier.issn0169-5002
dc.identifier.urihttp://hdl.handle.net/11351/7972
dc.descriptionALK inhibitors; Ceritinib; Ribociclib
dc.description.abstractBackground Preclinical data show that the combination of an ALK inhibitor (ALKi) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) may act synergistically to overcome drug resistance mechanisms. Here, we assessed the safety, tolerability, and preliminary clinical activity of ceritinib, an ALKi in combination with ribociclib, a CDK4/6i, in patients with ALK-rearranged non–small cell lung cancer (NSCLC). Methods This was a multicenter, open-label, phase Ib/II dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) for ceritinib plus ribociclib therapy. Results Twenty-seven adult patients with ALK-rearranged advanced NSCLC with an ECOG PS ≤ 2 were enrolled into five cohorts to receive various dose combinations of ceritinib (range, 300–450 mg/day) and ribociclib (range, 100–300 mg/day). Median age of patients was 57 years. MTDs were not reached in this study. Enrollment into phase Ib was terminated early and phase II was not opened due to changes in the ALK-rearranged NSCLC treatment landscape. Ceritinib 300 mg/day and ribociclib 200 mg/day (3-weeks-on/1-week-off schedule) was identified as the RP2D. Among the 27 evaluable patients, the overall response rate (ORR) was 37.0% (95% CI, 19.4–57.6) and median progression-free survival (mPFS) was 21.5 months (95% CI, 5.5–25.0). At RP2D, the ORR was 50.0%, disease control rate was 75%, and mPFS was 24.8 months (95% CI, 5.5–25.1). Safety profile of the combination therapy was consistent with single-agent safety data. Conclusion Combination of ceritinib and ribociclib showed clinical activity with a manageable safety profile in patients with advanced ALK-rearranged NSCLC.
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesLung Cancer;166
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectPulmons - Càncer - Tractament
dc.subjectProteïnes quinases - Inhibidors
dc.subject.meshCarcinoma, Non-Small-Cell Lung
dc.subject.mesh/drug therapy
dc.subject.meshProtein Kinase Inhibitors
dc.subject.mesh/adverse effects
dc.titlePhase Ib/II study of ceritinib in combination with ribociclib in patients with ALK-rearranged non–small cell lung cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1016/j.lungcan.2022.02.010
dc.subject.decscarcinoma de pulmón de células no pequeñas
dc.subject.decs/farmacoterapia
dc.subject.decsinhibidores de proteínas cinasas
dc.subject.decs/efectos adversos
dc.relation.publishversionhttps://doi.org/10.1016/j.lungcan.2022.02.010
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Santoro A, Simonelli M] Department of Biomedical Sciences, Humanitas University, Milan, Italy. IRCCS Humanitas Research Hospital–Humanitas Cancer Center, Milan, Italy. [Su WC] Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan. [Navarro A, Felip E] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Yang JCH] National Taiwan University Cancer Center, Taipei, Taiwan. [Ardizzoni A] IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
dc.identifier.pmid35298959
dc.identifier.wos000789861800003
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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