Multi-maintenance olaparib therapy in relapsed, germline BRCA1/2-mutant high-grade serous ovarian cancer (MOLTO): a phase II trial
Authors
Morgan, Robert DavidClamp, 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
Affiliation
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester,Issue Date
2023
Metadata
Show full item recordAbstract
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 ResearchDOI
10.1158/1078-0432.CCR-22-3282PubMed ID
36799931Additional Links
https://dx.doi.org/10.1158/1078-0432.CCR-22-3282Type
OtherLanguage
enae974a485f413a2113503eed53cd6c53
10.1158/1078-0432.CCR-22-3282