Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/4/915 |
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| author | Andres Poveda Raquel Lopez-Reig Ana Oaknin Andres Redondo Maria Jesus Rubio Eva Guerra Lorena Fariñas-Madrid Alejandro Gallego Victor Rodriguez-Freixinos Antonio Fernandez-Serra Oscar Juan Ignacio Romero Jose A. Lopez-Guerrero |
| author_facet | Andres Poveda Raquel Lopez-Reig Ana Oaknin Andres Redondo Maria Jesus Rubio Eva Guerra Lorena Fariñas-Madrid Alejandro Gallego Victor Rodriguez-Freixinos Antonio Fernandez-Serra Oscar Juan Ignacio Romero Jose A. Lopez-Guerrero |
| author_sort | Andres Poveda |
| collection | DOAJ |
| description | 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 (<i>n</i> = 46), endometrial (<i>n</i> = 26), and triple-negative breast cancer (<i>n</i> = 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 (<i>p</i> = 0.055). Globally, the total number of LOHs might be associated with the ORR (<i>p</i> =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. |
| first_indexed | 2024-03-09T22:23:56Z |
| format | Article |
| id | doaj.art-40f736661759425aa979e1ea3903bb8b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:23:56Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-40f736661759425aa979e1ea3903bb8b2023-11-23T19:08:27ZengMDPI AGCancers2072-66942022-02-0114491510.3390/cancers14040915Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational StudyAndres Poveda0Raquel Lopez-Reig1Ana Oaknin2Andres Redondo3Maria Jesus Rubio4Eva Guerra5Lorena Fariñas-Madrid6Alejandro Gallego7Victor Rodriguez-Freixinos8Antonio Fernandez-Serra9Oscar Juan10Ignacio Romero11Jose A. Lopez-Guerrero12Oncogynecologic Department, Initia Oncology, Hospital Quironsalud, Avda Blasco Ibañez, 14, 46010 Valencia, SpainLaboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, 46009 Valencia, SpainMedical Oncology Department, Vall d’Hebron University Hospital, Vall d´Hebron Institute of Oncology (VHIO), 08035 Barcelona, SpainMedical Oncology Department, Hospital Universitario La Paz-IdiPAZ, Universidad Autónoma de Madrid (UAM), 28049 Madrid, SpainMedical Oncology Department, Universitary Hospital Reina Sofia, 14004 Cordoba, SpainMedical Oncology, Hospital Universitario Ramón y Cajal, 28034 Madrid, SpainMedical Oncology Department, Vall d’Hebron University Hospital, Vall d´Hebron Institute of Oncology (VHIO), 08035 Barcelona, SpainMedical Oncology Department, Hospital Universitario La Paz-IdiPAZ, Universidad Autónoma de Madrid (UAM), 28049 Madrid, SpainMedical Oncology Department, Vall d’Hebron University Hospital, Vall d´Hebron Institute of Oncology (VHIO), 08035 Barcelona, SpainLaboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, 46009 Valencia, SpainMedical Oncology, Pivotal SLU, 28023 Madrid, SpainMedical Oncology, Fundacion Instituto Valenciano de Oncologia, 46009 Valencia, SpainLaboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, 46009 Valencia, SpainWe 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 (<i>n</i> = 46), endometrial (<i>n</i> = 26), and triple-negative breast cancer (<i>n</i> = 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 (<i>p</i> = 0.055). Globally, the total number of LOHs might be associated with the ORR (<i>p</i> =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.https://www.mdpi.com/2072-6694/14/4/915ovarian cancerendometrial cancerlurbinectedinolaparibgenomic instability |
| spellingShingle | Andres Poveda Raquel Lopez-Reig Ana Oaknin Andres Redondo Maria Jesus Rubio Eva Guerra Lorena Fariñas-Madrid Alejandro Gallego Victor Rodriguez-Freixinos Antonio Fernandez-Serra Oscar Juan Ignacio Romero Jose A. Lopez-Guerrero Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study Cancers ovarian cancer endometrial cancer lurbinectedin olaparib genomic instability |
| title | Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study |
| title_full | Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study |
| title_fullStr | Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study |
| title_full_unstemmed | Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study |
| title_short | Phase 2 Trial (POLA Study) of Lurbinectedin plus Olaparib in Patients with Advanced Solid Tumors: Results of Efficacy, Tolerability, and the Translational Study |
| title_sort | phase 2 trial pola study of lurbinectedin plus olaparib in patients with advanced solid tumors results of efficacy tolerability and the translational study |
| topic | ovarian cancer endometrial cancer lurbinectedin olaparib genomic instability |
| url | https://www.mdpi.com/2072-6694/14/4/915 |
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