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Found 1 Presentation For Request "832P"
832P - GEICO1601-ROLANDO trial: A multicentric single arm phase II clinical trial to evaluate the combination of olaparib and pegylated liposomal doxorubicin for platinum-resistant ovarian cancer
- Jose Alejandro Perez Fidalgo (Valencia, Valencia, Spain)
Abstract
Background
The benefit of olaparib (OLA) in platinum-resistant ovarian cancer (PROC) patients (pts) with BRCA wild-type tumors is scarce. The combination with DNA-damaging chemotherapy may be synergistic and improve the activity of OLA.
Methods
Patients with high-grade serous or endometrioid and one previous PROC (between 28 days-6 months after last platinum) were eligible regardless of BRCA status. Pts had received ≤ 4 previous lines (up to 5 in BRCA-mut pts), and primary PROC was only allowed in the presence of BRCA-mut otherwise at least one previous platinum-sensitive relapse was required. Pts received 6 cycles of OLA 300 mg b.i.d + pegylated liposomal doxorubicin (PLD) 40 mg/m2 (PLD40) intravenously q28d followed by OLA 300 mg b.i.d. until progression or toxicity. Due to high toxicity a protocol amendment was performed to reduce PLD to 30 mg/m2 (PLD30). The primary endpoint was progression-free survival at 6 months (6mPFS) by RECIST 1.1 and the threshold for futility was 40% 6mPFS.
Results
31 pts (ITT cohort) received at least 1 cycle, but only 20 pts were in the per protocol cohort (PP). ITT median age was 58,03 years, ECOG 0/1: 32.3/67.7%, serous subtype 84%. PP median age was 60 y.o., ECOG 0/1: 25%/75%, serous subtype: 85% and BRCA status was WT/mut/unk: 75%/20%/5%. Median of prior lines was 2 (1-4). Median number of cycles was 4.2 (0.9-19.5) for OLA and 4 (2-6) for PLD. After a median follow-up of 9.29 (0.9-21.3) mo, the 6mPFS in the ITT population was 44.2% (95%CI 28.7-68.1%) and median PFS 5.32 mo. In the PP cohort 6mPFS was 46.1% (95%CI 27.2-78.3) with a median PFS of 5.42 mo (4-12). 65% pts achieved stable disease and 25% partial response (overall control rate 90%). 74% of ITT pts had a Grade ≥3 adverse event (AE), being the most frequent neutropenia/anemia/febrile neutropenia: 39%/19%/10%. SAEs were less frequent in PLD30 (N=14) than in PLD40 (n=17): 21%/47%, as well as PLD delays 30/40: 30%/45% and reductions 30/40: 10%/25%.
Conclusions
OLA+PLD combination has shown clear activity with 46% 6mPFS rate in PROC regardless of BRCA status. PLD at 30 mg/m2 was better tolerated in the combination.
Clinical trial identification
EudraCT: 2016-004850-14; NCT03161132.
Legal entity responsible for the study
Grupo Español de Investigación en Cáncer de Ovario (GEICO).
Funding
AstraZeneca.
Disclosure
J.A. Perez Fidalgo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Ability Pharma; Advisory/Consultancy: Clovis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: GSK. A. Cortés: Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony: Roche; Research grant/Funding (institution): Roche-Genentech; Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy: Ferrer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Corcept Therapeutics; Research grant/Funding (institution): Seattle Genetics. Y. García: Advisory/Consultancy: Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK/Tesaro; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. A. Oaknin: Honoraria (self): AbbVie, Inc.; Honoraria (self), Honoraria (institution): Amgen, S.A; Honoraria (self): AstraZeneca; Honoraria (self), Honoraria (institution): Clovis Oncology; Honoraria (self), Honoraria (institution): F. Hoffman - La Roche Ltd; Honoraria (self): Genmab; Honoraria (self): GlaxoSmithKline SA; Honoraria (self), Honoraria (institution): ImmunoGen; Honoraria (self): Merck Sharp & Dohme; Honoraria (self), Honoraria (institution): Pharma Mar, SA; Honoraria (self): prIME; Honoraria (self), Honoraria (institution): Tesaro; Honoraria (institution): AbbVie Deutschland; Honoraria (institution): Ability Pharmaceuticals; Honoraria (institution): Advaxis Inc.; Honoraria (institution): Aeterna Zentaris; Honoraria (institution): Aprea Therapeutics AB; Honoraria (institution): EISAI limited LTD; Honoraria (institution): Regeneron Pharmaceuticals; Honoraria (institution): Merck Sharp & Dohme de España SA; Honoraria (institution): Millennium Pharmaceuticals Inc; Honoraria (institution): BMS; Leadership role: GEICO; Leadership role: GCIG Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO; Leadership role: ESMO Faculty Member Gynaecological for ESMO 2018 and Chair of Gynaecological Tack for ESMO 2019; Non-remunerated activity/ies: ESMO; Non-remunerated activity/ies: ASCO; Non-remunerated activity/ies: GCIG; Non-remunerated activity/ies: SEOM; Non-remunerated activity/ies: GOG. A. Redondo: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): PharmaMar; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: GSK; Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Amgem; Research grant/Funding (institution): Eisai; Non-remunerated activity/ies, PI of phase II Cecilia study (carboplatin-paclitaxel and bevacizumab in advanced cervical cancer), sponsored by Roche: Roche; Leadership role, Member of Executive Board and Secretary of Spanish Group of Ovarian Cancer Research: GEICO. A. González Martín: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy: Pfizer/Merck; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy, Speaker Bureau/Expert testimony: PharmaMar; Advisory/Consultancy: MSD; Advisory/Consultancy: Genmab; Advisory/Consultancy: Oncoinvent; Honoraria (institution), Financial support for ANITA/GEICO trial: Roche; Honoraria (institution), Financial support for ANITA/GEICO trial: Tesaro; Non-remunerated activity/ies, Principal Investigator of PRIMA study sponsored by Tesaro: Tesaro; Leadership role, Chairman: GEICO; Leadership role, Chairman: ENGOT. All other authors have declared no conflicts of interest.