A phase 2 trial exploring the significance fi cance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib

被引:1
作者
Liu, Joyce F. [1 ]
Xiong, Niya [2 ]
Wenham, Robert M. [3 ]
Wahner-Hendrickson, Andrea [4 ]
Armstrong, Deborah K. [5 ]
Chan, Nancy [6 ,17 ]
O'Malley, David M. [7 ]
Lee, Jung-Min [8 ]
Penson, Richard T. [9 ]
Cristea, Mihaela C. [10 ,18 ]
Abbruzzese, James L. [11 ]
Matsuo, Koji [12 ]
Olawaiye, Alexander B. [13 ]
Barry, William T. [2 ,19 ]
Cheng, Su-Chun [2 ]
Polak, Madeline [1 ]
Swisher, Elizabeth M. [14 ]
Shapiro, Geoffrey I. [1 ]
Kohn, Elise C. [8 ,15 ]
Ivy, S. Percy [16 ]
Matulonis, Ursula A. [1 ]
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA
[2] Dana Farber Canc Inst, Dept Data Sci, Boston, MA USA
[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Gynecol Oncol, Tampa, FL USA
[4] Mayo Clin, Dept Med Oncol, Rochester, MN USA
[5] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Dept Med Oncol, Baltimore, MD USA
[6] Rutgers Canc Inst New Jersey, Dept Med Oncol, New Brunswick, NJ USA
[7] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH USA
[8] NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD USA
[9] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA USA
[10] City Hope Natl Med Ctr, Comprehens Canc Ctr, Dept Med Oncol, Duarte, CA USA
[11] Duke Canc Inst, Dept Med Oncol, Durham, NC USA
[12] Univ Southern Calif, Dept Obstet & Gynecol, Keck Sch Med, Los Angeles, CA USA
[13] Univ Pittsburgh, Med Ctr, Dept OBGYN, Pittsburgh, PA USA
[14] Univ Washington, Dept Obstet & Gynecol, Seattle, WA USA
[15] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD USA
[16] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD USA
[17] NYU Langone Hlth, Dept Med Oncol, New York, NY USA
[18] Regeneron Pharmaceut Inc, Tarrytown, NY USA
[19] Rho, Durham, NC USA
关键词
Ovarian cancer; Anti-angiogenic; PARP inhibitor; Cediranib; Olaparib; DOWN-REGULATION; FALLOPIAN-TUBE; MAINTENANCE THERAPY; SOMATIC MUTATIONS; BRCA1/2; MUTATION; DOUBLE-BLIND; RECURRENT; PERITONEAL; CARCINOMA; RUCAPARIB;
D O I
10.1016/j.ygyno.2024.05.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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). 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. 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). 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. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
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页码:105 / 112
页数:8
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