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.