Concordance Between Tumor and Germline BRCA Status in High-Grade Ovarian Carcinoma Patients in the Phase III PAOLA-1/ENGOT-ov25 Trial.

Abstract

BACKGROUND:

PAOLA1 is a phase III study assessing olaparib maintenance therapy in advanced high-grade ovarian carcinoma patients responding to first-line platinum-taxane-based chemotherapy plus bevacizumab as standard of care. Randomization was stratified by treatment outcome and tumor BRCA1/2 status (tBRCA) at screening.

METHODS:

tBRCA was tested on formalin-fixed, paraffin-embedded tumor blocks on 5 French platforms using 2 next-generation sequencing methods based either on hybrid capture or amplicon technology. One of the exploratory objectives was to assess the concordance between germline (gBRCA) and tBRCA testing in French patients. gBRCA testing was performed on blood samples on the same platforms.

RESULTS:

From May 2015 to July 2017, tBRCA tests were performed for 1176 screened patients. Only 52 (4.4%) tumor samples were noncontributive. The median interval between reception of the tumor sample and availability of the tBRCA status result was 37 days (range = 8-260). A pathogenic variant was reported in 27.1% tumor samples (319 of 1176 screened patients). tBRCA and gBRCA testing were performed for 451 French patients with negative results for both tests in 306 patients (67.8%) and positive results for both tests in 85 patients (18.8%). Only 1 large genomic rearrangement of BRCA1 was detected, exclusively in the blood sample. Interestingly, tBRCA testing revealed 6.4% of pathogenic variant (29 of 451) not detected by gBRCA testing.

CONCLUSIONS:

tBRCA testing is an appropriate tool with an acceptable turnaround time for clinical practice and a low failure rate, ensuring reliable identification of patients likely to benefit from poly(ADP-ribose) polymerase inhibitor therapy.

• Authors: Céline Callens, Dominique Vaur, Isabelle Soubeyran, Etienne Rouleau, Pierre-Alexandre Just, Erell Guillerm, Lisa Golmard, Nicolas Goardon, Nicolas Sevenet, Odile Cabaret, Philipp Harter, Antonio Gonzalez-Martin, Keiichi Fujiwara, Sabrina Chiara Cecere, Nicoletta Colombo, Christian Marth, Ignace Vergote, Johanna Maenpaa, Eric Pujade-Lauraine, Isabelle Ray-Coquard
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 113 Issue 7 Pg. 917-923 (07 01 2021) ISSN: 1460-2105 [Electronic] United States
• PMID: 33372675 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].

Chemical References

• BRCA1 Protein
• BRCA2 Protein
• Phthalazines
• Poly(ADP-ribose) Polymerase Inhibitors
• Bevacizumab

Topics

• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Bevacizumab (therapeutic use)
• Carcinoma, Ovarian Epithelial
• Female
• Germ Cells (pathology)
• Germ-Line Mutation
• Humans
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Phthalazines (therapeutic use)
• Poly(ADP-ribose) Polymerase Inhibitors (therapeutic use)