2026-04-17T22:52:37Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/78792024-11-01T01:13:56Zcom_2072_378070com_2072_378040col_2072_378092

Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study Poveda, Andres Oaknin Benzaquen, Ana Mazaltob Rubio, Maria Jesus Guerra, Eva Fariñas Madrid, Lorena Rodriguez Freixinos, Victor López-Reig, Raquel Redondo Sanchez, Andres Institut Català de la Salut [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 Vall d'Hebron Barcelona Hospital Campus Càncer - Tractament Avaluació de resultats (Assistència sanitària) DISEASES::Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ENFERMEDADES::neoplasias Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia Endometrial cancer; Genomic instability; Olaparib Cáncer endometrial; Inestabilidad genómica; Olaparib Càncer d'endometri; Inestabilitat genòmica; Olaparib 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. This trial was sponsored by AstraZeneca and PharmaMar, including supply of the drugs used in this study. 2022-07-20T11:04:32Z 2022-07-20T11:04:32Z 2022-02-12 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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. 2072-6694 https://hdl.handle.net/11351/7879 10.3390/cancers14040915 35205662 000763155700001 eng Cancers;14(4) https://doi.org/10.3390/cancers14040915 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf MDPI Scientia