PAOLA-01 is a randomized placebo-controlled, international phase III study, assessing olaparib in maintenance therapy in advanced high grade ovarian carcinoma patients responding to 1st line platinum-taxane-based chemotherapy plus bevacizumab. Stratification is performed on treatment outcome and on tumoral BRCA1/2 status (tBRCA) at screening. As secondary objective, the consistency between germline (gBRCA) and tBRCA testing is being explored.
This study is planned to recruit 762 pts in Europe and 24 in Japan. tBRCA is tested on FFPE tumor block within 5 French national institutional platforms using 2 different next-generation sequencing methods based either on capture or on re-sequencing technology. For French pts, gBRCA testing is performed in parallel in the same platforms.
Since May 2015, 1181 pts have been screened and 662 pts randomized. tBRCA status was assessed in 962 samples with a median turn around time of 40 days (range 8-260). Only 44(4.6%) tumor samples were non-informative (too low tumor cellularity), 8 using capture method and 36 by re sequencing respectively. A deleterious variant (DV) was reported in 279 (29%) samples (191 (68%) in BRCA1, 87 (31%) in BRCA2 and one in both genes). Twelve variants of unknown significance were identified for BRCA2 and 13 for BRCA1. For the 384 French pts, where both gBRCA & tBCRA testing was performed in parallel we report the mutation rate detection in the Table below. Of note, only one large genomic rearrangement of BRCA1 was detected in blood sample exclusively.
tBRCA testing is a reliable tool for clinical trials with acceptable delay for clinical practice. Proportion of tBRCA testing failure is low and consistency with germ line testing adequate for routine practice.Table:
|French Cohort||gBRCA + (%)||gBRCA-(%)||Total (%)|
|tBRCA +||67 (17)||23 (6)||90 (24)|
|tBRCA -||1 (0.3)||270 (70)||271 (71)|
|Inconclusive tumor testing||1 (0.3)||22 (5,7)||23 (6)|
|total||69 (18)||315 (82)||384 (100)|
Clinical trial identification
EudractCT: 2014-004027-52 NCT02477644 First received: June 18, 2015
Legal entity responsible for the study
AstraZeneca and Roche
I. Soubeyran: Fees from Astra-Zeneca, Roche and ThermoFisher; advisory boards fees from Astra-Zeneca, Pfizer and MSD for intervening expert. P. Harter: Consulting or advisory role: Roche, AstraZeneca; research funding: AstraZeneca. A. Gonzalez Martin: Consultant and speaker for Roche and AstraZeneca. K. Fujiwara: AstraZeneca as an advisory board, travel expense and research grant. Also has COI with Chugai-Roche for research grant. S. Pignata: Honoraria: AstraZeneca, Roche; consulting or advisory role: AstraZeneca, Roche; research funding: Roche. N. Colombo: Advisory board: Roche and AstraZeneca; Out of this trial, advisory board: Tesaro, Clovis, Pharmamar, Advaxis, Pfizer. C. Marth: Honoraria: Roche, AstraZeneca, Pfizer; consulting or advisory role: Roche, AstraZeneca, Pfizer Travel, accomodations, expenses: Roche, AstraZeneca and Pfizer. I. Vergote: Consulting or advisory board: AstraZeneca Z. J. Mäenpää: Consulting or advisory role: Roche, AMGEN, SOBI, AstraZeneca Travl, accomdations, expenses: GSK, SOBI, Roche, AstraZeneca. E. Pujade-Lauraine: Consulting or advisory role: Roche, AstraZeneca, Pfizer; speaker\'s bureau: Roche, AstraZeneca, Pfizer; travel, accomodations, expenses: Roche, AstraZeneca. I. Ray-Coquard: Honoraria: Roche, Pharmamar, AstraZeneca; consulting or advisory board: Roche, Pharmamar, AstraZeneca, Advixis; travel, accomodations, expenses: Roche, Pharmamar, AstraZeneca. All other authors have declared no conflicts of interest.