Around 15-25% of ovarian cancer (OC) patients carry germ-line mutation in BRCA1 or BRCA2
genes. Recent evidences showed that OC women with germline BRCA1/2 mutations (gBRCAmut) have
an improved survival and higher platinum-sensitivity compared to BRCA1/2 naive (BRCAwt).
Interestingly, disease appearance in BRCAmut women is more diffuse than in BRCAwt cases, with
significantly higher peritoneal tumour load.
Nonetheless, BRCAmut women additionally show a higher benefit of platinum-based neoadjuvant
chemotherapy (NACT) plus interval debulking surgery compared with BRCAwt women in terms of
clinical and pathological responses, suggesting that BRCA mutational status might be used as
a molecular tool to personalize treatment in high-grade serous ovarian cancer (HGSOC)
OLAPARIB in BRCA mutation carriers Olaparib is a potent oral poly (ADP-ribose) polymerase
(PARP) inhibitor that causes synthetic lethality in BRCA1/2-deficient tumour cells. In
patients with platinum-sensitive relapsed serous ovarian cancer, olaparib maintenance
treatment significantly improved the duration of progression-free survival compared with
placebo (hazard ratio [HR] 0.35 [95% CI (confidence interval) 0.25-0.49]; p<0.0001), with the
greatest clinical benefit in patients with BRCA mutations (HR 0.18 [95% CI 0.10-0.31];
Preclinical data suggest that olaparib might also potentiate the efficacy of DNA-damaging
chemotherapies, including platinum-containing drugs such as carboplatin.
In a recent phase Ib/II study, olaparib plus weekly carboplatin and paclitaxel in relapsed
ovarian cancer patients was shown to be safe, well tolerated and effective, especially in
germline BRCA mutated (gBRCAmut) patients.
Possibly, the addition of a PARP inhibitor (olaparib) to NACT in HGSOC patient with germline
or somatic BRCA1/2 mutation is able to increase the pathological complete response rate to
conventional chemotherapy. Combination of intermittent olaparib with weekly carboplatin and
paclitaxel might achieve a higher pathological response rate, with an acceptable toxicity
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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