dc.contributor
Institut Català de la Salut
dc.contributor
[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.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Poveda, Andres
dc.contributor.author
Oaknin Benzaquen, Ana Mazaltob
dc.contributor.author
Rubio, Maria Jesus
dc.contributor.author
Guerra, Eva
dc.contributor.author
Fariñas Madrid, Lorena
dc.contributor.author
Rodriguez Freixinos, Victor
dc.contributor.author
López-Reig, Raquel
dc.contributor.author
Redondo Sanchez, Andres
dc.date.issued
2022-07-20T11:04:32Z
dc.date.issued
2022-07-20T11:04:32Z
dc.date.issued
2022-02-12
dc.identifier
Poveda 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
https://hdl.handle.net/11351/7879
dc.identifier
10.3390/cancers14040915
dc.identifier
000763155700001
dc.description.abstract
Endometrial cancer; Genomic instability; Olaparib
dc.description.abstract
Cáncer endometrial; Inestabilidad genómica; Olaparib
dc.description.abstract
Càncer d'endometri; Inestabilitat genòmica; Olaparib
dc.description.abstract
We 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.description.abstract
This trial was sponsored by AstraZeneca and PharmaMar, including supply of the drugs used in this study.
dc.format
application/pdf
dc.format
application/pdf
dc.relation
Cancers;14(4)
dc.relation
https://doi.org/10.3390/cancers14040915
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Càncer - Tractament
dc.subject
Avaluació de resultats (Assistència sanitària)
dc.subject
DISEASES::Neoplasms
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Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
ENFERMEDADES::neoplasias
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.title
Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
