Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial

Autor: Robert D. Morgan, Andrew R. Clamp, Daniel J. White, Marcus Price, George J. Burghel, W. David J. Ryder, Reem D. Mahmood, Alexander D. Murphy, Jurjees Hasan, Claire L. Mitchell, Zena Salih, Chelsey Wheeler, Emma Buckley, Joanna Truelove, Georgia King, Yasmina Ainaoui, Sanjeev S. Bhaskar, Joseph Shaw, D. Gareth R. Evans, Bedirhan Kilerci, Simon P. Pearce, Gerard Brady, Caroline Dive, James P.B. O'Connor, Andrew J. Wallace, Dominic G. Rothwell, Richard J. Edmondson, Gordon C. Jayson
Rok vydání: 2023
Předmět:
Zdroj: Clinical Cancer Research. :OF1-OF10
ISSN: 1557-3265
1078-0432
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: