A new study presented at the American Society of Clinical Oncology (ASCO) 2018 meeting shows that in metastatic destructive-resistant prostate cancer (metastatic) patients who had received docetaxel chemotherapy castration-resistant prostate cancer (mCRPC) patients who had received docetaxel chemotherapy, treatment with olaparib, a PARP inhibitor, in combination with abiraterone significantly prolonged radiologic progression-free survival (rPFS) compared with the anti-androgen drug abiraterone alone. The treatment with olaparib (olaparib, a PARP inhibitor) in combination with abiraterone significantly prolonged radiologic progression-free survival (rPFS, survival time without signs of tumor progression on imaging).
This is the first clinical finding that a PARP inhibitor combined with an androgen synthesis inhibitor produces significant efficacy, and the results are exciting. The results were also published in the Lancet Oncology, a top international medical journal.
What is olaparib?
What is olaparib?
Olaparib, a targeted cancer therapy developed by the University of Cambridge, is 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. Olaparib, a type of PARP inhibitor, is used in this way to destroy cancer cells.
Back in 2014, the FDA (food and drug administration) approved olaparib capsules for advanced ovarian cancer with BRCA mutations that had received 3 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.
Clinical evidence for olaparib for prostate cancer
There is currently one phase 2 clinical trial of olaparib for prostate cancer. This randomized, placebo-controlled study looked at patients with mCRPC who received docetaxel chemotherapy and whose tumors did not have homologous recombination repair mutations.
142 patients with mCRPC were randomized to two groups, one treated with olaparib and abiraterone in combination and one treated with abiraterone alone.
-
Prolonged imaging progression-free survival of 5.6 months
The results of the study showed that the combination group had a significant advantage in extending progression-free survival in patients. The median rPFS was 13.8 months in the olaparib combined with abiraterone group compared with 8.2 months in the abiraterone alone group, meaning that the combination group prolonged rPFS by 5.6 months.
Overall survival also improved, but not significantly
However, overall survival (OS) was similar in both groups, with a median overall survival of 22.7 months for patients in the olaparib-combined-abiraterone group and 20.9 months in the abiraterone alone group, a nonsignificant difference.
Significantly more adverse reactions, treatment interruptions
The combination group had a significantly higher rate of adverse events, including some serious adverse events, compared with the monotherapy group; there was also a higher rate of treatment discontinuation due to adverse events in the combination group (30% vs 10%). The researchers concluded that this was not unexpected, because usually there is an increase in adverse events with the addition of another treatment regimen.
The investigators concluded that although the combination resulted in some compromise in patient tolerability, it still has some clinical value because of the significant increase in efficacy.
In conclusion, although the results look promising, more clinical studies are needed to validate them and questions about discontinuation rates need to be addressed. If data from future phase 3 clinical trials support the current conclusions, then olaparib would be promising for approval in prostate cancer treatment.