1. Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation and with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial
- Author
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Lee, Jung-Min, Moore, Richard G, Ghamande, Sharad, Park, Min S, Diaz, John P, Chapman, Julia, Kendrick, James, Slomovitz, Brian M, Tewari, Krishnansu S, Lowe, Elizabeth S, Milenkova, Tsveta, Kumar, Sanjeev, Dymond, Mike, Brown, Jessica, and Liu, Joyce F
- Subjects
Ovarian Cancer ,Rare Diseases ,Clinical Trials and Supportive Activities ,Orphan Drug ,Cancer ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.2 Cellular and gene therapies ,6.1 Pharmaceuticals ,Adolescent ,Adult ,BRCA1 Protein ,Bevacizumab ,Carcinoma ,Ovarian Epithelial ,Female ,Germ Cells ,Germ-Line Mutation ,Humans ,Indoles ,Mutation ,Neoplasm Recurrence ,Local ,Ovarian Neoplasms ,Phthalazines ,Piperazines ,Poly(ADP-ribose) Polymerase Inhibitors ,Quinazolines ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeThe efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer.Patients and methodsPARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm ovarian cancer, ECOG performance status of 0-2, and ≥3 prior lines of therapy received cediranib 30 mg once daily plus olaparib 200 mg twice daily in this single-arm, multicenter, phase IIb trial. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST 1.1. Progression-free survival (PFS), overall survival (OS), and safety and tolerability were also examined.ResultsSixty patients received cedi/ola, all of whom had confirmed non-gBRCAm status. Patients had received a median of four lines of chemotherapy; most (88.3%) had received prior bevacizumab. ORR by ICR was 15.3%, median PFS was 5.1 months, and median OS was 13.2 months. Forty-four (73.3%) patients reported a grade ≥3 adverse event (AE), with one patient experiencing a grade 5 AE (sepsis), considered unrelated to the study treatment. Dose interruptions, reductions, and discontinuations due to AEs occurred in 55.0%, 18.3%, and 18.3% of patients, respectively. Patients with high global loss of heterozygosity (gLOH) had ORR of 26.7% [4/15; 95% confidence interval (CI), 7.8-55.1], while ORR was 12.5% (4/32; 95% CI, 3.5-29.0) in the low gLOH group.ConclusionsClinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with ovarian cancer despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies.
- Published
- 2022