A Severance Hospital team has confirmed that BRCA (Breast Cancer) gene-mutated ovarian cancer patients who took poly ADP ribose polymerase (PARP) inhibitors experience reduced therapeutic efficacy when the disease recurs.

A Severance Hospital research team -- led by Professors Lee Jung-yun (left) and Park Jun-sik -- confirmed that the PARP inhibitors reduced the efficacy of anticancer therapies in the relapsed patients of BRCA-mutated ovarian cancer who had taken the inhibitors previously.
A Severance Hospital research team -- led by Professors Lee Jung-yun (left) and Park Jun-sik -- confirmed that the PARP inhibitors reduced the efficacy of anticancer therapies in the relapsed patients of BRCA-mutated ovarian cancer who had taken the inhibitors previously.

An increasing number of patients receive maintenance treatment using PARP inhibitors to prevent the recurrence of epithelial ovarian cancer with BRCA mutations. PARP inhibitor-based maintenance therapies have proven efficacy in reducing the recurrence rate and prolonging disease-free survival in ovarian cancer patients in large-scale phase 3 studies.

However, a post-analysis result of the SOLO-2 clinical study announced during the 2020 European Cancer Society (ESMO) showed that the follow-up treatment’s efficacy was lower in patients who took the PARP inhibitor olaparib than in patients who had not taken it when cancer recurred.

Professors Lee Jung-yun of the Department of Obstetrics and Gynecology and Park Jun-sik of the Department of Biomedical Sciences led the study.

The team conducted a study on 197 patients with epithelial ovarian cancer with BRCA mutation who received secondary chemotherapy at Severance Hospital, Seoul National University Hospital, and Samsung Medical Center from January 2012 to June 2020.

The research team compared and analyzed the subjects by dividing them into 105 patients who received olaparib maintenance treatment and 92 patients who did not receive it after platinum-based chemotherapy.

Afterward, the team investigated whether or not recurrence occurred after treatment in both groups, response to tertiary chemotherapy after recurrence, and the period until the next recurrence.

As a result, the team confirmed that the group receiving olaparib maintenance treatment significantly prolonged progression-free survival (PFS) compared to the control group.

Also, as previously confirmed, the PFS of the olaparib maintenance group was 17.8 months, while the control group was 10.8 months.

However, the period from the tertiary chemotherapy to the next recurrence was 7.9 months in the group receiving olaparib maintenance treatment, compared to 13.6 months in the group that did not receive PARP maintenance treatment.

Also, the objective treatment response rate to the tertiary chemotherapy of the relapsed patients receiving olaparib maintenance treatment was 20.4 percent, far lower than the control group’s 66.7 percent.

“The study showed that there is an urgent need to develop a treatment that is more effective than the existing platinum chemotherapy for epithelial ovarian cancer patients who have relapsed after taking PARP inhibitors,” Professor Lee said. “To increase the survival rate of patients with progressively increasing PARP inhibitor resistance-recurrent ovarian cancer, we are making efforts to present the optimal treatment through clinical trials and translational studies of new drugs.”

Gynecologic Oncology published the result of the study.

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