According to an article published online first in the Lancelot Oncology, findings revealed the potential of olaparib to treat patients with more common sporadic (non-hereditary) tumors which could offer a new treatment option for one of the most deadly cancers in women. For the first time the PARP inhibitor, olaparib, that has shown promise in women with an inherited mutation in their BRCA1 or BRCA2 gene (accounting for about 5-10% of breast and ovarian cancer cases) reduced tumor sizes in a much wider group of ovarian cancer patients without these BRCA gene mutations.

Leading author Karen Gelmon from the BC Cancer Agency in Vancouver, Canada, explains,

“Olaparib represents a promising therapeutic option for patients with this aggressive malignant disease for whom treatment options are limited to toxic chemotherapies.”

Olaparib works by blocking the activity of a protein called Poly (ADP ribose) polymerase (PARP), both of which are involved in DNA repair. Cancer cells are prevented from repairing their DNA (improving the effectiveness of DNA-damaging chemotherapy) and causing them to die (a process known as synthetic lethality*) if PARP in a tumor, that already lacks a BRCA, is inhibited.

It remained unknown until now whether olaparib could also be effective in a broader group of sporadic breast and ovarian cancers that might share similar DNA repair deficiencies, such as triple-negative breast cancer and high-grade serous ovarian cancer.

The phase 2 trial was conducted to assess olaparib’s effectiveness in the treatment of breast and ovarian cancer without BRCA gene mutations. 92 patients of which 65 had ovarian cancer and 26 suffered from breast cancer received olaparib 400mg twice daily for a 4-week duration. The study took place between July 2008 and September 2009 with patients being classified according to their BRCA1 and BRCA2 mutation status.

Researchers discovered that 41% with BRCA mutations showed a substantial shrinkage in the size of their tumors compared with 24% of patients without mutations among women with ovarian cancer. None of the patients with breast cancer showed an objective response.

All patients had a generally good tolerance towards Olaparib with most side effects being mild, including fatigue, nausea, vomiting, and decreased appetite.

In a concluding statement the authors say “new treatments targeting DNA repair mechanisms seems to provide new hope for treatment of ovarian cancer.”

Melinda Telli from Stanford University School of Medicine in California, USA discusses the potential of this new class of genetically-targeted drugs in a comment where she remarks:

“For the first time, activity of a PARP inhibitor as monotherapy in women with advanced high-grade serous ovarian cancer who do not have a germline BRCA1 or BRCA2 mutation [has been shown]. This finding not only suggests new therapeutic possibilities for women with this aggressive type of ovarian cancer, but also importantly confirms the hypothesis that subpopulations of patients with common sporadic tumors can be targeted effectively with PARP inhibitor therapy.”

Written by Petra Rattue