Impact of BRCA1/2 Mutations on the Efficacy of Secondary Cytoreductive Surgery
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ORIGINAL ARTICLE – GYNECOLOGIC ONCOLOGY
Impact of BRCA1/2 Mutations on the Efficacy of Secondary Cytoreductive Surgery Felipe Leonardo Estati, MD1, Rafaela Pirolli, MD1, Viviane Teixeira Loiola de Alencar, MD1, Adriana Regina Gonc¸alves Ribeiro, MD, MSc1, Maria Nirvana Formiga, MD, PhD1,2, Giovana Tardin Torrezan, PhD3, Dirce Maria Carraro, PhD3, Andrea Paiva Gadelha Guimara˜es, MD, MSc1, Glauco Baiocchi, MD, PhD4, and Alexandre Andre´ Balieiro Anasta´cio da Costa, MD, PhD1 1
Department of Medical Oncology, A.C. Camargo Cancer Center, Sa˜o Paulo, SP, Brazil; 2Department of Oncogenetics, A.C. Camargo Cancer Center, Sa˜o Paulo, SP, Brazil; 3Genomics and Molecular Biology Group, A.C. Camargo Cancer Center, Sa˜o Paulo, SP, Brazil; 4Department of Gynecology Oncology, A.C. Camargo Cancer Center, Sa˜o Paulo, SP, Brazil
ABSTRACT Background. Phase III trials evaluating the role of secondary cytoreductive surgery (SCS) in recurrent ovarian cancer have pointed to the importance of patient selection. Two studies showed conflicting results regarding the benefit of SCS in BRCA1/2 mutation carriers. Our aim was to evaluate the impact of SCS on recurrent ovarian cancer according to BRCA1/2 status. Methods. All patients with ovarian carcinoma with platinum-sensitive recurrent disease and tested for BRCA1/2 germline mutations were included. Cox regression and log rank test were used to evaluate the impact of SCS on progression-free survival (PFS) and the influence of BRCA1/2 mutations on the effect of SCS. Results. 127 patients were included, 45.6% were treated with SCS and chemotherapy and 54.3% treated with chemotherapy only. Patients treated with SCS were younger, presented better performance status, had lower CA125, and had a longer platinum-free interval. In multivariate analysis SCS was associated with longer PFS (HR 0.42, 95% CI 0.25–0.72, p = 0.002). BRCA1/2 mutations
Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-020-09366-w) contains supplementary material, which is available to authorized users. Ó Society of Surgical Oncology 2020 First Received: 14 June 2020 Accepted: 10 October 2020 A. A. B. A. da Costa, MD, PhD e-mail: [email protected]
were found in 35 patients (27.5%), and 11.8% of patients were treated with PARP inhibitors. Although not statistically significant, both BRCA1/2 wild type patients (PFS: 21.6 vs 18.4 months; p = 0.114) and BRCA1/2 mutation carriers (PFS: 23.1 vs 18.2 months, p = 0.193) appeared to derive benefit from SCS. Discussion. The present study suggests a benefit of SCS irrespective of BRCA1/2 status among patients mostly not treated with PARP inhibitor. Further data on post hoc analysis from the phase III trials are warranted to confirm whether BRCA1/2 mutated patients should be selected for SCS.
Ovarian cancer is the most lethal gynecological cancer and most diagnosed patients will recur during follow-up.1,2 The main treatment for recurrent ovarian carcinoma is systemic therapy with chemotherapy and targeted therapies. F
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