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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorPoveda, Andres
dc.contributor.authorLópez-Reig, Raquel
dc.contributor.authorOaknin benzaquen, Ana Mazaltob
dc.contributor.authorRedondo Sanchez, Andres
dc.contributor.authorRubio, Maria Jesus
dc.contributor.authorGuerra, Eva
dc.contributor.authorFariñas Madrid, Lorena
dc.contributor.authorRodriguez Freixinos, Victor
dc.date.accessioned2022-07-20T11:04:32Z
dc.date.available2022-07-20T11:04:32Z
dc.date.issued2022-02-12
dc.identifier.citationPoveda A, Lopez-Reig R, Oaknin A, Redondo A, Rubio MJ, Guerra E, et al. Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study. Cancers. 2022 Feb 12;14(4):915.
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/11351/7879
dc.descriptionEndometrial cancer; Genomic instability; Olaparib
dc.description.abstractWe hypothesized that the combination of olaparib and lurbinectedin maximizes DNA damage, thus increasing its efficacy. The POLA phase 1 trial established the recommended phase 2 dose of lurbinectedin as being 1.5 mg (day 1) and that of olaparib as being 250 mg/12 h (days 1–5) for a 21-day cycle. In phase 2, we explore the efficacy of the combination in terms of clinical response and its correlation with mutations in the HRR genes and the genomic instability (GI) parameters. Results: A total of 73 patients with high-grade ovarian (n = 46), endometrial (n = 26), and triple-negative breast cancer (n = 1) were treated with lurbinectedin and olaparib. Most patients (62%) received ≥3 lines of prior therapy. The overall response rate (ORR) and disease control rate (DCR) were 9.6% and 72.6%, respectively. The median progression-free survival (PFS) was 4.54 months (95% CI 3.0–5.2). Twelve (16.4%) patients were considered long-term responders (LTR), with a median PFS of 13.3 months. No clinical benefit was observed for cases with HRR gene mutation. In ovarian LTRs, although a direct association with GI and a total loss of heterozygosity (LOH) events was observed, the association did not reach statistical significance (p = 0.055). Globally, the total number of LOHs might be associated with the ORR (p =0.074). The most common grade 3–4 toxicities were anemia and thrombocytopenia, in 6 (8.2%) and 3 (4.1%) patients, respectively. Conclusion: The POLA study provides evidence that the administration of lurbinectedin and olaparib is feasible and tolerable, with a DCR of 72.6%. Different GI parameters showed associations with better responses.
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofseriesCancers;14(4)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectCàncer - Tractament
dc.subjectAvaluació de resultats (Assistència sanitària)
dc.subject.meshNeoplasms
dc.subject.mesh/drug therapy
dc.titlePhase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3390/cancers14040915
dc.subject.decsneoplasias
dc.subject.decs/farmacoterapia
dc.relation.publishversionhttps://doi.org/10.3390/cancers14040915
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Poveda A] Oncogynecologic Department, Initia Oncology, Hospital Quironsalud, Valencia, Spain. [Lopez-Reig R] Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. IVO-CIPF Joint Research Unit of Cancer, Príncipe Felipe Research Center (CIPF), Valencia, Spain. [Oaknin A, Fariñas-Madrid L] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Redondo A] Medical Oncology Department, Hospital Universitario La Paz-IdiPAZ, Universidad Autónoma de Madrid (UAM), Madrid, Spain. [Rubio MJ] Medical Oncology Department, Universitary Hospital Reina Sofia, Cordoba, Spain. [Guerra E] Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. [Rodriguez-Freixinos V] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
dc.identifier.pmid35205662
dc.identifier.wos000763155700001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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