open access: Profile of olaparib in the treatment of advanced ovarian cancer Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Thursday, May 19, 2016

open access: Profile of olaparib in the treatment of advanced ovarian cancer



open access
 Published 18 April 2016

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Ongoing research

SOLO-1 and SOLO-2 are multicenter, double-blind studies of olaparib 300 mg bid versus placebo in patients with high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer. Both SOLO-1 and SOLO-2 have primary outcomes of progression-free survival by response evaluation criteria in solid tumors (RECIST) criteria in olaparib 300 mg twice daily monotherapy maintenance compared to placebo. The study population of SOLO-1 is BRCA-mutated high-risk advanced ovarian cancer patients who achieved complete or partial response with first-line platinum chemotherapy, whereas the population of SOLO-2 is BRCA-mutated relapsed ovarian cancer patients who achieved complete or partial response with platinum chemotherapy. In SOLO-1, the patients will receive olaparib versus placebo for up to 2 years or until objective response by RECIST criteria and the treatment may continue beyond 2 years for those with stable disease or progression. Patients in SOLO-2 will receive olaparib versus placebo until progression by RECIST criteria or as long as they are benefiting from treatment and do not meet other criteria for discontinuation.16,17
The current FDA approval for olaparib is for patients who have received three or more prior lines of chemotherapy. A recent study by Marques et al investigated whether the administration of chemotherapy affected intratumoral PARP expression. Tissue samples were obtained from three cohorts, totaling 313 high-grade serous ovarian cancers. PARP1 expression was measured by immunohistochemistry and Western blot protein analysis. Samples from patients who had undergone chemotherapy had significantly lower protein expression than chemotherapy-naïve tumor samples. Of 15 samples from patients which had both pre- and postchemotherapy (carboplatin and paclitaxel), six had absent PARP1 expression and eight had reduced PARP1 levels postchemotherapy. The clinical significance of this change in PARP1 expression is unknown; however, the dynamic interaction of PARP1 and chemotherapy should be taken into consideration in future studies.18 It is possible that the use of olaparib before exposure to multiple lines of chemotherapy would be a more effective use.

Conclusion

Olaparib is a well-tolerated oral chemotherapeutic agent that has FDA approval for the treatment of ovarian cancer in patients with germline BRCA 1/2 mutations who have received three or more prior lines of chemotherapy. In the future, development of assays for function of homologous recombination may help to identify patients without a germline BRCA 1/2 mutation who would also benefit from treatment with olaparib. Further studies will also help delineate the optimal timing and setting of olaparib administration.

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