S Intidhar Labidi-Galy1, Thibault de La Motte Rouge2, Olfa Derbel3, Anita Wolfer4, Elsa Kalbacher5, Timothée Olivier6, Jean-Damien Combes7, Ketty Heimgartner-Hu6, Olivier Tredan8, Hemerson Guevara8, Pierre-Etienne Heudel8, Thibaut Reverdy8, Fernando Bazan5, Viola Heinzelmann-Schwarz9, Mathias Fehr10, Victoire de Castelbajac11, Pauline Vaflard11, Louise Crivelli12, Valerie Bonadona13, Valeria Viassolo6, Adrien Buisson14, Lisa Golmard15, Manuel Rodrigues16, Isabelle Ray-Coquard17. 1. Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland; Department of Medecine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: intidhar.labidi-galy@hcuge.ch. 2. Department of Medical Oncology, Centre Eugène Marquis, Rennes, France. 3. Institut du Cancer Jean Mermoz, Lyon, France. 4. Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 5. Division of Medical Oncology, CHU Besancon, Besancon, France. 6. Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland. 7. International Agency for Research on Cancer, Lyon, France. 8. Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 9. Department of Gynecology, Basel University Hospital, Basel, Switzerland. 10. Frauenklinik, Kantonsspital Frauenfeld, Frauenfeld, Switzerland. 11. Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France. 12. Division of Cancer Genetics, Centre Eugène Marquis, Rennes, France. 13. Unit of Prevention and Genetic Epidemiology, UMR CNRS 5558, Centre Léon Bérard, Lyon, France. 14. Division of Molecular Genetics, Hospices Civiles de Lyon, Lyon, France. 15. Division of Genetics, Pôle de Médecine diagnostique et théranostique, Institut Curie, Paris, France. 16. Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France; INSERM U830, institut Curie, PSL Research University, Paris, France. 17. Department of Medical Oncology, Centre Léon Bérard, Lyon, France; University Claude Bernard (UCBL Lyon1), Lyon, France.
Abstract
OBJECTIVE: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice. METHODS: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy. RESULTS: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125. CONCLUSIONS: Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy.
OBJECTIVE: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice. METHODS: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy. RESULTS: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125. CONCLUSIONS: Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy.
Authors: Ana Oaknin; Amit M Oza; Domenica Lorusso; Carol Aghajanian; Andrew Dean; Nicoletta Colombo; Johanne I Weberpals; Andrew R Clamp; Giovanni Scambia; Alexandra Leary; Robert W Holloway; Margarita Amenedo Gancedo; Peter C Fong; Jeffrey C Goh; David M O'Malley; Deborah K Armstrong; Susana Banerjee; Jesus García-Donas; Elizabeth M Swisher; Terri Cameron; Lara Maloney; Sandra Goble; Jonathan A Ledermann; Robert L Coleman Journal: Cancer Med Date: 2021-09-21 Impact factor: 4.452