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    Multi-maintenance olaparib therapy in relapsed, germline BRCA1/2-mutant high-grade serous ovarian cancer (MOLTO): a phase II trial

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    Authors
    Morgan, Robert David
    Clamp, Andrew R
    White, Daniel J
    Price, Marcus
    Burghel, G. J.
    Ryder, W. D. J.
    Mahmood, Reem D
    Murphy, Alexander D
    Hasan, Jurjees
    Mitchell, Claire L
    Salih, Zena
    Wheeler, Chelsey
    Buckley, Emma
    Truelove, Joanna
    King, G.
    Ainaoui, Y.
    Bhaskar, S. S.
    Shaw, J.
    Evans, D. G. R.
    Kilerci, Bedirhan
    Pearce, Simon P
    Brady, Ged
    Dive, Caroline
    O'Connor, James P B
    Wallace, A. J.
    Rothwell, Dominic G
    Edmondson, Richard J
    Jayson, Gordon C
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    Affiliation
    Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester,
    Issue Date
    2023
    
    Metadata
    Show full item record
    Abstract
    Purpose: A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown. Patients and methods: Phase II trial with two entry points (EP1, EP2). Patients were recruited prior to rechallenge platinum. Patients with relapsed, gBRCAm-HGSOC were enrolled at EP1 if they were PARPi-naïve. Patients enrolled at EP2 had received their first course of olaparib prior to trial entry. EP1 patients were retreated with olaparib after RECIST complete/partial response (CR/PR) to platinum. EP2 patients were retreated with olaparib ± cediranib after RECIST CR/PR/stable disease to platinum and according to the platinum-free interval. Co-primary outcomes were the proportion of patients who received a second course of olaparib and the proportion who received olaparib retreatment for ≥6 months. Functional homologous recombination deficiency (HRD), somatic copy-number alteration (SCNA), and BRCAm reversions were investigated in tumor and liquid biopsies. Results: Twenty-seven patients were treated (EP1 = 17, EP2 = 10), and 19 were evaluable. Twelve patients (63%) received a second course of olaparib and 4 received olaparib retreatment for ≥6 months. Common grade ≥2 adverse events during olaparib retreatment were anemia, nausea, and fatigue. No cases of MDS/AML occurred. Mean duration of olaparib treatment and retreatment differed (12.1 months vs. 4.4 months; P < 0.001). Functional HRD and SCNA did not predict PFS. A BRCA2 reversion mutation was detected in a post-olaparib liquid biopsy. Conclusions: A second course of olaparib can be safely administered to women with gBRCAm-HGSOC but is only modestly efficacious. See related commentary by Gonzalez-Ochoa and Oza, p. 2563.
    Citation
    Morgan RD, Clamp AR, White DJ, Price M, Burghel GJ, Ryder WDJ, et al. Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial. Clinical Cancer Research. 2023 Jul;29(14):2602-11. PubMed PMID: WOS:001043746600001.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/626532
    DOI
    10.1158/1078-0432.CCR-22-3282
    PubMed ID
    36799931
    Additional Links
    https://dx.doi.org/10.1158/1078-0432.CCR-22-3282
    Type
    Other
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.CCR-22-3282
    Scopus Count
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