Olaparib, a targeted cancer therapy developed by the University of Cambridge, is also the first poly ADP-ribose polymerase (PARP) inhibitor. It can fight cancers with mutations in the BRCA1/ 2 (breast cancer susceptibility gene 1/2) gene, including ovarian, breast, and prostate cancers.
The anti-cancer principle of PARP inhibitors is related to mutations in the BRCA1/2 gene. When cells divide, DNA is replicated, but if DNA is damaged by errors in replication, the cell often goes on to die, as do cancer cells.
The BRCA1/2 gene and PARP are the two pathways responsible for DNA damage repair, and if the cancer cell itself has a BRCA1/2 mutation, the use of a PARP inhibitor can block both pathways of DNA repair, ultimately causing apoptosis due to continued DNA damage. This is how olaparib, a PARP inhibitor, is used to destroy cancer cells.
Back in 2014, the FDA (food and drug administration) approved olaparib capsules for BRCA-mutated advanced ovarian cancer that had received three or more chemotherapy treatments; in 2017, it approved olaparib tablets for recurrent epithelial ovarian cancer that has responded completely or partially to platinum-based chemotherapy. ovarian cancer. In January 2018, olaparib was approved for the treatment of HER2-negative metastatic breast cancer with a BRCA mutation.
Olaparib improves survival in ovarian cancer patients, and the numbers are exciting!
A double-blind, randomized phase 3 clinical study enrolled 295 patients with ovarian, fallopian tube, or primary peritoneal cancer and randomly assigned them to the olaparib or placebo groups.
The trial found that the median progression-free survival in the olaparib group was 19.1 months, more than a threefold increase over the 5.5 months in the placebo group! And the Olaparib group also had approximately 3 times the progression-free survival rate of the control group! And in patients carrying the BRCA1/2 mutation, median progression-free survival with olaparib remained significantly longer than in the placebo group (19.3 months vs. 5.5 months)!
In addition, the rate of grade 3-5 adverse reactions to olaparib was low, with the most common grade 1-2 adverse reactions being nausea, fatigue, vomiting, abdominal pain, and diarrhea, and a good safety profile.
In addition to patients with BRCA mutations, another study included a subset of subjects with BRCA-unmutated mutations (BRCA mutated:unmutated=1:1). The study found that the median progression-free survival in the olaparib group was 8.4 months, which remained significantly longer than the 4.8 months in the placebo group, and that olaparib reduced the patients’ risk of disease progression by 65%. That said, Olaparib may also have a therapeutic effect in patients with BRCA-unmutated disease.
It was on the basis of these two trials that the FDA approved olaparib tablets in August 2017 for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers. In addition, many ongoing clinical studies are exploring the role of olaparib alone or in combination with other drugs for different types of ovarian cancer, and expect them to lead to equally exciting results.
Conclusion
To date, the FDA has approved three PARP inhibitors for marketing. Olaparib, the first PARP inhibitor to be approved, has brought impressive survival benefits to patients with ovarian cancer and offers a new treatment option for patients with ovarian cancer that carries a BRCA mutation or even an unmutated BRCA.
In December 2017, Olaparib was submitted for marketing in China, and in February 2018, the State Drug Administration included Olaparib for platinum-sensitive recurrent ovarian cancer in its priority review and approval process, giving it accelerated approval.