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. 2022 Jun 6:13:863956.
doi: 10.3389/fgene.2022.863956. eCollection 2022.

Clinical Benefits of Olaparib in Mexican Ovarian Cancer Patients With Founder Mutation BRCA1-Del ex9-12

Dolores Gallardo-Rincón  1   2 , Edgar Montes-Servín  1 , Gabriela Alamilla-García  1   2 , Elizabeth Montes-Servín  1 , Antonio Bahena-González  1   2 , Lucely Cetina-Pérez  3   4 , Flavia Morales Vásquez  2 , Claudia Cano-Blanco  2 , Jaime Coronel-Martínez  2 , Ernesto González-Ibarra  1 , Raquel Espinosa-Romero  1   2 , Rosa María Alvarez-Gómez  3   5 , Abraham Pedroza-Torres  5   6 , Denisse Castro-Eguiluz  4   6
Affiliations

Clinical Benefits of Olaparib in Mexican Ovarian Cancer Patients With Founder Mutation BRCA1-Del ex9-12

Dolores Gallardo-Rincón et al. Front Genet. .

Abstract

Background: Ovarian cancer (OC) is gynecologic cancer with the highest mortality rate. It is estimated that 13-17% of ovarian cancers are due to heritable mutations in BRCA1 and BRCA2. The BRCA1 (BRCA1-Del ex9-12) Mexican founder mutation is responsible for 28-35% of the cases with ovarian cancer. The aim was to describe the PFS of OC patients treated with olaparib, emphasizing patients carrying the Mexican founder mutation (BRCA1-Del ex9-12). Methods: In this observational study, of 107 patients with BRCAm, 35 patients were treated with olaparib from November 2016 to May 2021 at the Ovarian Cancer Program (COE) of Mexico; patient information was extracted from electronic medical records. Results: Of 311 patients, 107 (34.4%) were with BRCAm; 71.9% (77/107) were with BRCA1, of which 27.3% (21/77) were with BRCA1-Del ex9-12, and 28.1% (30/107) were with BRCA2 mutations. Only 35 patients received olaparib treatment, and the median follow-up was 12.87 months. The PFS of BRCA1-Del ex9-12 was NR (non-reach); however, 73% of the patients received the treatment at 36 vs. 11.59 months (95% CI; 10.43-12.75) in patients with other BRCAm (p = 0.008). Almost 50% of patients required dose reduction due to toxicity; the most frequent adverse events were hematological in 76.5% and gastrointestinal in 4%. Conclusion: Mexican OC BRCA1-Del ex9-12 patients treated with olaparib had a significant increase in PFS regardless of the line of treatment compared to other mutations in BRCA.

Keywords: BRCA mutation; Mexican founder mutation; epithelial ovarian cancer; large rearrangements; progression-free survival.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Patient enrollment flowchart. Flowchart summarizes patient enrollment and sub-analysis groups.
FIGURE 2
FIGURE 2
Patient PFS analysis. (A) Histogram per patient shows the follow-up of each patient undergoing olaparib treatment and time after progression. Patients are grouped according to the presence of the Mexican founder mutation and other mutations organized by the lines of treatment received before olaparib maintenance therapy. Patients with BRCA1 founder mutation (BRCA1-Del ex9-12) (purple bars); patients with other BRCA mutations: second line (turquoise bars); third line (yellow bars); and patients in fourth line or more (red bars). (B) Progression-free survival comparison between BRCA1-Del ex9-12 and other BRCA mutations of patients undergoing olaparib maintenance therapy. Kaplan–Meier curve of PFS. Patients with BRCA1 founder mutation (BRCA1-Del ex9-12) (purple line); patients with other BRCA mutations (turquoise line). (C) Progression-free survival comparison between lines of treatment of the other BRCA mutations of patients undergoing olaparib maintenance therapy. Kaplan–Meier curve of PFS. Patients in second line (turquoise line), third line (yellow line), and patients in fourth line or more (red line).
See this image and copyright information in PMC

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