Treating ovarian cancers with PARP inhibitors

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Published: 8 May 2019
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Lisa Marie Juden - Dana-Farber Cancer Institute, Boston, MA

Lisa Marie Juden speaks to ecancer at ONS 2019 about how PARP inhibitors are used to treat ovarian cancers.

She explains how PARP inhibitors work and which drugs are currently approved for which patients.

Lisa concludes by describing the benefits of oncology nurses being aware of PARP inhibitors.

PARP inhibitors are poly(ADP-ribose) polymerase inhibitors, known as PARPs. They are used in gynaecological cancers for maintenance therapy, recently approved. What that is is when patients have double stranded DNA the DNA can have a single strand break. Usually patients will have a BRCA gene that comes and fixes that break.

PARP inhibitors were first used as a trial in patients with BRCA mutations, BRCA1 and 2 mutations, who are females who have a deficiency that have a higher risk for both ovarian and breast cancers. When you have a BRCA deficiency you do not have the ability to repair DNA as effectively as someone who doesn’t. So within their cancer cells, which is specific to ovarian and breast cancer cells, when they have a single strand break with the BRCA the BRCA can’t be there to fix that single strand break. So what happens is the cancer cells that are trying to grow and repopulate their DNA call for a back-up and the back-up is PARP. The PARP will then go and back up and try to fix that DNA and therefore the cancer is able to grow. However, in BRCA patients if we inhibit the PARP and block it from responding then we can potentially kill the cancer cell because without the BRCA gene or having the BRCA mutation which these women have, as well as inhibiting the PARP as a back-up plan to help their DNA, then in theory there is cancer cell death.
So this was originally studied with BRCA patients with one of the PARP inhibitors called olaparib. It was originally approved for women who had multiple lines of treatment and it was approved as a treatment and/or maintenance after that. That was a few years ago, back in 2014. More recently a few other PARP inhibitors, niraparib and rucaparib, were approved in the maintenance setting for this type of patients with the exception of niraparib that was approved for any patients or discovered that all women with ovarian cancer would benefit from having PARP inhibition. Then even more recently, in November of 2018, the PARP was approved in ovarian cancer after first line treatment.

So it originally started as primarily just for BRCA mutated women, we now know that it helps all women with ovarian cancer, whether they have a BRCA mutation or a somatic BRCA mutation meaning their tumour has some sort of mutation in it. Then also as well anyone with a recurrent ovarian cancer.

Why is it important for oncology nurses to be aware of PARP inhibitors?

I would say the importance is in the future for gynaecological cancers using PARP as a maintenance has been a really big breakthrough for us to maintain as a maintenance medication, to keep the disease away for as long as we possibly can and have our patients have the best quality of life in that time. It’s very important that this is widespread across the country because maybe more metropolitan areas where people are more comfortable using PARP it’s more prevalent. So to spread the word, especially with nursing, to educate our nurses to feel comfortable with this type of medication and this use of a maintenance treatment after chemotherapy. So not everything is just chemotherapy and done.
Also, it’s important to know for our nurses that the PARP is a targeted therapy and the target is quite specific to the gyn cancer in the recurrent setting, so that they become more comfortable with knowledge of what a PARP is and that the adverse effects, once worked through, they can be maintained and hopefully resolved and that just improves quality of life.