PARP* inhibitors (PARPi) are a new family of drugs being used in the treatment of ovarian cancer. This kind of cancer treatment has a different focus than something like immunotherapy that targets the body’s immune system. PARP inhibitors target the ability of a cancer cell to repair its damaged DNA and either survive or die. PARP is a protein inside cells that helps repair damage to the cell DNA. If the cell can repair itself, it will survive and grow. If the cell cannot repair itself, it will die. So, the PARP “inhibitor” stops a cancer cell from repairing its DNA which causes cell death and prevents tumour growth.
There are actually two mechanisms within the cell that help repair DNA – PARP and a tumour suppressor gene. Tumour suppressor genes are normal genes that regulate cell division, repair DNA mistakes, or tell cells when to die. When tumor suppressor genes don’t work properly, cells can grow out of control, which can lead to cancer. (Source: cancer.org)
The BRCA1 and BRCA2 genes (“BRCA”) are tumour suppressor genes. A mutated or faulty BRCA1 or BRCA2 gene is no longer able to function normally and cannot repair DNA damage. A mutation in the BRCA1 or BRCA2 gene increases the risk for both ovarian and breast cancer.
Clinical trials have shown that women with a BRCA1 or BRCA2 gene mutation respond best to treatment with PARP inhibitors because both mechanisms that control DNA damage repair are not functioning. Therefore, this leads to greater tumour cell death and reduction in tumour size and growth. But evidence shows that women who do not have a BRCA mutation can also respond to treatment with a PARP inhibitor. The reason for this is not fully understood at this time but results are encouraging. So, for now, in a strange way, it seems more advantageous to have a BRCA mutation at least in terms of the potential response to treatment with PARPi.
Are there other advantages to PARP inhibitors?
Several. PARPi are oral medications so they can be taken at home and eliminate the time, energy and cost associated with travel back and forth to the cancer centre. There are no needles, IVs or ports so the administration of the drug is less invasive to the body and there are fewer side effects compared to chemotherapy drugs.
Most important, PARPi, compared with standard treatment options, can increase a period of remission so that the individual can experience greater quality of life for a longer period of time before a recurrence. This is called “progression free survival (PFS)” and you will hear this term more and more in the future.
An Update on Specific PARP Inhibitor Drugs – Lynparza and Zejula
Lynparza (olaparib)
Lynparza is a PARP inhibitor that can be prescribed as a maintenance drug following treatment for a recurrence or initial diagnosis of high grade epithelial ovarian, fallopian tube and primary peritoneal cancers for those with a BRCA mutation. It must be administered no later than 8 weeks after completion of platinum-based therapy. However, access to the drug varies depending on a number of factors.
For those whose high-grade serous ovarian cancer has recurred:
Lynparza is now publicly funded in all provinces in Canada except Prince Edward Island for those who meet the specific requirements. The promising results from the early clinical trials were based on patients with a BRCA mutation and platinum sensitive disease (recurrence occurred six months or more from end of first line treatment). Therefore, the request for and ultimate funding approved by the government was based on this specific criteria. Ovarian Cancer Canada continues to advocate for the remaining province to add Lynparza to its formularies for this indication.
For those with an initial diagnosis of high-grade serous ovarian cancer:
In April 2019, AstraZeneca (AZ), the manufacturer of Lynparza, submitted a request to the pan-Canadian Oncology Drug Review (pCODR) and INESSS in Quebec for funding approval for Lynparza as a maintenance protocol after initial diagnosis and first line treatment of platinum sensitive ovarian cancer for patients with a BRCA mutation. This is exciting news, but the process to secure the public funding of a drug and add it to the formularies in each province can take up to 18 months. Thankfully, the AstraZeneca & Merck Oncology Patient Support Program will now cover the full cost of Lynparza during this approval process! There are certain criteria to qualify for this program (and it is only available for 12 months) but we encourage you to speak with your oncologist to learn more and to enroll if you are eligible.
Zejula (niraparib)
Zejula is a new PARP inhibitor manufactured by Glaxo Smith Kline (GSK). Clinical trials for Zejula were not limited to patients with a BRCA mutation, therefore, when approved in Canada, it will be available to all women with high-grade serous, platinum sensitive ovarian cancer, regardless of BRCA status. This is great news and the results of the clinical trials are very promising.
For those whose high-grade serous ovarian cancer has recurred:
In June 2019, Health Canada approved the use of Zejula as a monotherapy (use of only one drug at a time) for the maintenance treatment of recurrent, platinum sensitive ovarian cancer. This approval is based on the results from the NOVA clinical trial. The next step is for Glaxo Smith Kline to make a submission to pCODR (INESSS in Quebec) for funding approval. Hopefully, that will happen in the near future!
For those with an initial diagnosis of high-grade serous ovarian cancer:
The PRIMA clinical trial for Zejula investigated the use of Zejula as maintenance after first line treatment of platinum sensitive ovarian cancer, regardless of BRCA status. This clinical trial is now closed and the results have not yet been released.
*PARP refers to Poly (ADP-ribose) polymerase.