Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation and with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial.
Clinical cancer research : an official journal of the American Association for Cancer Research
washington; swedish; swedish cancer
PURPOSE: The efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with non-germline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer (OC).
PATIENTS AND METHODS: PARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm OC, 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.
RESULTS: Sixty 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% CI 7.8-55.1%), while ORR was 12.5% (4/32; 95% CI 3.5-29.0%) in the low gLOH group.
CONCLUSIONS: Clinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with OC despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies.
Women & Children
Obstetrics & Gynecology
Lee, Jung-Min; Moore, Richard G; Ghamande, Sharad; Park, Min; 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, "Cediranib in combination with olaparib in patients without a germline BRCA1/2 mutation and with recurrent platinum-resistant ovarian cancer: Phase IIb CONCERTO trial." (2022). Articles, Abstracts, and Reports. 6412.