TY - JOUR
T1 - Cediranib in Combination with Olaparib in Patients without a Germline BRCA1/2 Mutation and with Recurrent Platinum-Resistant Ovarian Cancer
T2 - Phase IIb CONCERTO Trial
AU - Lee, Jung Min
AU - Moore, Richard G.
AU - Ghamande, Sharad
AU - Park, Min S.
AU - Diaz, John P.
AU - Chapman, Julia
AU - Kendrick, James
AU - Slomovitz, Brian M.
AU - Tewari, Krishnansu S.
AU - Lowe, Elizabeth S.
AU - Milenkova, Tsveta
AU - Kumar, Sanjeev
AU - Dymond, Mike
AU - Brown, Jessica
AU - Liu, Joyce F.
N1 - Publisher Copyright:
© 2022 The Authors.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Purpose: The 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 Methods: PARP inhibitor-naive 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. 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% 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. Conclusions: Clinical 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.
AB - Purpose: The 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 Methods: PARP inhibitor-naive 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. 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% 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. Conclusions: Clinical 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.
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U2 - 10.1158/1078-0432.CCR-21-1733
DO - 10.1158/1078-0432.CCR-21-1733
M3 - Article
C2 - 35917514
AN - SCOPUS:85139535643
SN - 1078-0432
VL - 28
SP - 4186
EP - 4193
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 19
ER -