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A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2024 Aug; Vol. 187, pp. 105-112. Date of Electronic Publication: 2024 May 17. - Publication Year :
- 2024
-
Abstract
- Objective: Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD).<br />Methods: Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity.<br />Results: In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23).<br />Conclusions: Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Female
Middle Aged
Aged
Adult
Homologous Recombination
Progression-Free Survival
Aged, 80 and over
Carcinoma, Ovarian Epithelial drug therapy
Carcinoma, Ovarian Epithelial genetics
Indoles
Phthalazines administration & dosage
Piperazines administration & dosage
Ovarian Neoplasms drug therapy
Ovarian Neoplasms genetics
Ovarian Neoplasms pathology
Drug Resistance, Neoplasm genetics
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Antineoplastic Combined Chemotherapy Protocols pharmacology
Neoplasm Recurrence, Local drug therapy
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local pathology
Quinazolines administration & dosage
Quinazolines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6859
- Volume :
- 187
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 38759516
- Full Text :
- https://doi.org/10.1016/j.ygyno.2024.05.002