학술논문
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.
Document Type
Academic Journal
Author
Liu JF; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America. Electronic address: joyce_liu@dfci.harvard.edu.; Xiong N; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, United States of America.; Wenham RM; Department of Gynecologic Oncology, Moffitt Cancer Center, Tampa, FL, United States of America.; Wahner-Hendrickson A; Department of Medical Oncology, Mayo Clinic, Rochester, MN, United States of America.; Armstrong DK; Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, United States of America.; Chan N; Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States of America.; O'Malley DM; Department of Obstetrics and Gynecology, The Ohio State University, Columbus, OH, United States of America.; Lee JM; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States of America.; Penson RT; Department of Medical Oncology, Massachusetts General Hospital, Boston, MA, United States of America.; Cristea MC; Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, United States of America.; Abbruzzese JL; Department of Medical Oncology, Duke Cancer Institute, Durham, NC, United States of America.; Matsuo K; Department of Obstetrics & Gynecology, Keck School of Medicine of University of Southern California, Los Angeles, CA, United States of America.; Olawaiye AB; Department of OBGYN, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America.; Barry WT; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, United States of America.; Cheng SC; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, United States of America.; Polak M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America.; Swisher EM; Department of Obstetrics & Gynecology, University of Washington, Seattle, WA, United States of America.; Shapiro GI; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America.; Kohn EC; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States of America; Clinical Investigations Branch, NCI Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, United States of America.; Ivy SP; Investigational Drug Branch, NCI Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, United States of America.; Matulonis UA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States of America.
Source
Publisher: Academic Press Country of Publication: United States NLM ID: 0365304 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-6859 (Electronic) Linking ISSN: 00908258 NLM ISO Abbreviation: Gynecol Oncol Subsets: MEDLINE
Subject
Language
English
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).
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.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
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.
(Copyright © 2024 Elsevier Inc. All rights reserved.)