Céline Callens1, Dominique Vaur2, Isabelle Soubeyran3, Etienne Rouleau4, Pierre-Alexandre Just5, Erell Guillerm5, Lisa Golmard1, Nicolas Goardon2, Nicolas Sevenet3, Odile Cabaret4, Philipp Harter6, Antonio Gonzalez-Martin7, Keiichi Fujiwara8, Sabrina Chiara Cecere9, Nicoletta Colombo10, Christian Marth11, Ignace Vergote12, Johanna Maenpaa13, Eric Pujade-Lauraine14, Isabelle Ray-Coquard15. 1. Genetics Department, Institut Curie and Paris Sciences Lettres University, Paris, France. 2. Laboratoire de Biologie Clinique et Oncologique, Centre François Baclesse, Caen, France. 3. Biopathology Department, Institut Bergonié, Bordeaux, France. 4. Biopathology Department, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France. 5. Department of Pathological Anatomy and Cytology, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Paris, France, Genetics Department, Hôpital Universitaire Pitié-Salpétrière, Assistance Publique - Hôpitaux de Paris, Paris, France. 6. Obstetric and Gynecologic Department, Kliniken Essen Mitte, Essen, AGO De, Germany. 7. Oncology Department, Clínica Universidad de Navarra, Madrid, formerly MD Anderson Cancer Center, Madrid, GEICO, Spain. 8. Gynecologic Oncologic Department, Saitama Medical University, Saitama, GOTIC, Japan. 9. Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Mito Italy. 10. Gynecology Oncology Division, European Institute of Oncology, Milan, Mango Italy. 11. Obstetric and Gynecologic Department, Medical University of Innsbruck, AGO Au, Austria. 12. Gynecologic Oncologic Department, University Hospital Leuven, Department of Gynecologic oncology, Leuven Cancer Institute, Leuven, BGOG, Belgium. 13. Gynecologic Oncologic Department, Tampere University and University Hospital Cancer Centre, Tampere, NSGO, Finland. 14. ARCAGY Research, Paris, France. 15. Medical Oncology Department, Centre Léon Bérard and University, Claude Bernard Lyon 1, Lyon, GINECO, France.
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.
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.
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