A significant progression-free survival (PFS) improvement in all-comer patients (pts) with platinum-sensitive, relapsed (PSR), high-grade serous ovarian cancer supported the approval of olaparib (LynparzaTM) capsules as maintenance monotherapy (Ledermann et al NEJM 2012); these results were confirmed using the new olaparib tablet formulation in pts with a germline BRCA1/2 mutation (BRCAm) (Pujade-Lauraine et al SGO 2017). Pts with epithelial ovarian cancer (EOC) often retain platinum sensitivity despite progression on PARP inhibitor (PARPi) maintenance therapy. After relapse, it is unknown whether such pts could derive clinical benefit from olaparib retreatment. The OReO/ENGOT Ov-38 trial (NCT03106987; D0816C00014) will evaluate efficacy and safety of maintenance retreatment with olaparib tablets in all-comer pts with EOC.
OReO/ENGOT Ov-38 is a randomized, placebo-controlled multicentre trial of olaparib maintenance retreatment in pts with non-mucinous EOC, and a complete or partial response to their most recent platinum-based chemotherapy. Eligibility requires prior receipt of maintenance PARPi therapy, or prior participation by pts in a study with a PARPi experimental arm. Randomization 2:1 to olaparib (300 mg twice daily tablets) or matching placebo will be split across two cohorts (approximately 416 pts): pts with a known BRCAm in cohort one; BRCA wild-type pts in cohort two. Pts with a known BRCAm (germline or somatic) must provide a tumour sample (archival or fresh) and a blood sample for post-analysis BRCA testing. Primary endpoint is investigator-assessed PFS (RECIST v1.1). Cohorts are independently powered at 80% to detect a PFS benefit (assuming a hazard ratio [olaparib:placebo] of 0.5 [cohort one] or 0.65 [cohort two]) at the two-sided 5% level. Table lists the secondary endpoints, including outcome measures for health-related quality of life. Enrolment began in Q2 2017.Table:
987TiP Secondary endpoints
|TTP by GCIG criteria|
|PRO measures for HRQoL:|
|– Change from baseline in the TOI of the FACT-O|
|– Proportion of pts with an improved PRO score|
|– Best overall response (improved, no change, worsened, other)|
|– PRO deterioration-free survival|
FACT-O, Functional Assessment of Cancer Therapy – Ovarian; GCIG, Gynecologic Cancer InterGroup; HRQoL, health-related quality of life; OS, overall survival; PRO, Patient Reported Outcome; TDT, time from randomization to study treatment discontinuation, or death; TFST, time from randomization to first subsequent treatment commencement, or death; TOI, Trial Outcome Index; TSST, time from randomization to second subsequent treatment commencement, or death; TTP, time to progression
Clinical trial identification
Legal entity responsible for the study
AstraZeneca and ENGOT
E. Pujade-Lauraine: Received advisory board membership and honoraria from AstraZeneca and Pfizer, and advisory board membership, honoraria and speakers\' bureau membership from Roche. N. Colombo: Received a grant from AstraZeneca, and personal fees from AstraZeneca, Roche, Pharmamar, Clovis, Pfizer and Tesaro. R. Glasspool: AstraZeneca: travel, registration, and accommodation for a non-compensated advisory board in June 2016, and for ASCO 2017. Advisory boards for Clovis and Tesaro (2016) and a speaker at a ROCHE meeting in March 2017. F. Marme: Received honoraria for Scientific advisory boards etc from: Roche, AstraZeneca, Novartis, Pfizer, PharmaMar, Eisai, Genmoic Health. M.R. Mirza: Board of Directors: Karyopharm., Metamark Genetics, Sera Prognostics Inc. Consultant/Advisory: Advaxis, AstraZeneca, Boehringer Ingelheim, Cerulean, Clovis, Genmab, Karyopharm, Novocure, Pfizer, Roche, Tesaro Study grants: AstraZeneca, Boehringer Ingelheim, Clovis, Pfizer, Roche, Tesaro. A. Redondo: AstraZeneca: Honoraria and travel expenses. C. Blakeley, A. Milner: Employed as a contractor for AstraZeneca, but does not own stock. All other authors have declared no conflicts of interest.