PARP inhibitors and their side effects in solid tumour therapy

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Published: 8 May 2019
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Paula Anastasia - David Geffen School of Medicine at UCLA Los Angeles, USA

Paula Anastasia speaks to ecancer at ONS 2019 about the changing paradigms of treating solid tumours with PARP inhibitors.

She proposes that, in order to get patients to report their side effects to nurses, patients need to be better educated about the treatment the are receiving. She explains that some patients are hesitant to talk to oncology nurses about their side effects as the fear it will result in dose reductions or dose holding, which might mean less efficacy - but this is not the case.

Paula speaks about some of the PARP inhibitors available for not only ovarian cancer but also metastatic breast cancer, the importance of genetic testing and what might be next for these therapies.

This programme has been supported by an unrestricted educational grant from Pfizer. 

This morning myself and two co-presenters we talked about the changing paradigm with PARP inhibitors in solid tumours. So it’s not just for ovarian cancer but there is now an FDA approval for metastatic breast cancer. My session was focussed on how to manage adverse events related to these PARP inhibitors; it’s also important to ask clinicians to assess our patients and help them with instructing patients to have oral adherence. It’s also important to talk to patients about class effect of some of the common side effects, such as nausea, haematological toxicities and fatigue. Many of these are very manageable; we often have to dose reduce or dose hold and there is a preconceived myth that patients believe that possibly if we’re dose reducing we’re reducing efficacy.  But we remind our patients that they’ve received many cycles of IV chemotherapy that is based on their height and weight and so with oral medications we are giving them one dose fits all. So we really need to individualise and personalise that while monitoring our patients on a weekly and monthly basis, monitoring their blood counts and then monthly in follow-up. But the important thing that we do tell our patients is we can help you best by you reporting to us what your side effects are. Sometimes patients don’t want to tell us what their side effects are because they’re afraid we are going to dose reduce or hold their medication and that would potentially cause their cancer to grow. So there’s a lot of education and reassurance that we need to provide our patients. Also, hopefully, I was able to help the clinician be able to better educate their patients who are undergoing oral therapies with PARP inhibitors.

Why is it important to have a multidisciplinary team providing these treatments?

It’s really important for the nurses, the clinician, the advance practice nurse, the PA, to be involved in this. We work as a team with physicians but advanced practice nurses and nurses who are in the practice setting that they give chemotherapy because even though this isn’t chemotherapy it’s targeted treatment for DNA repair mechanisms. These patients, the nurses know these patients really well and we are able to help guide the physicians who are prescribing. Nurse practitioners also prescribe and physician assistants also have the ability to prescribe in certain states so it’s important when we individualise what is the patient’s past history and side effect profile with a prior IV chemotherapy? Did they have to have any dose reductions? Did they receive any blood transfusions? Did they receive growth factors when they received IV chemotherapy? This can be helpful going forward because those might be similar or at risk side effects that patients may have receiving a PARP inhibitor. Very manageable but it’s important to know what their past history is so we need to ask but also, with all due respect, the nurses tend to know these side effects better and remember them better because we’re the ones taking the phone calls, we’re the ones talking to the patients at the beside. So collaboratively and working together with the physician, being able to help them identify which patient and which PARP inhibitor might be a better choice.

Can you tell us about the PARP inhibitors that are currently FDA approved?

There are three PARP inhibitors approved for ovarian cancer – olaparib, rucaparib and niraparib. They all are approved for patients in the maintenance setting after frontline therapy, first recurrence and in remission. So they would have had two lines of prior chemo. Olaparib just received a new indication to receive maintenance therapy after finishing their frontline therapy, and that’s usually going to be with a taxane and a platinum, so the patient now is in a remission and they can get frontline maintenance therapy. So that’s a brand new indication and a little bit different than after the first relapse. Olaparib also just received approval for metastatic breast cancer in the second line setting or advanced for germline BRCA mutations.
So there is a fourth PARP inhibitor that just got FDA approved and this is only for breast cancer and it’s for metastatic breast cancer for patients that have HER2 negative and also that are germline BRCA mutation carriers. So there are a few things to sort out there and individualise in that care and the name of that drug is talazoparib and that’s a once daily oral capsule.

So the market is expanding and we know how important genetic counselling is and genetic testing but not just for the patient but also cascades, so testing the family as well, because clinical trials are ongoing now for not only with breast cancer, we have one indication, but in combination with chemotherapy and PARP inhibitors. Also we know that the BRCA2 is associated with pancreatic cancer and prostate cancer and there are ongoing trials that are looking very promising.  So it’s important that we are testing the family members also of these patients that have breast and ovarian cancer to see if we can prevent or at least help these patients live longer and better.

How do you see PARP inhibitors being used in the future?

PAPR inhibitors have set a new mainstream with ovarian cancer, especially for maintenance therapy. Number one, our patients didn’t live long enough thirty years ago to have a maintenance therapy and we are definitely extending lives and using PARP inhibitors earlier on. It’s interesting because when it was first FDA approved the first indication was in ovarian cancer third line treatment for patients with germ cell BRCA. So now we’ve moved that up even earlier so patients that are getting it earlier are having a history of less chemotherapy, therefore they have less side effects and they are tolerating it better. Now we have an indication using it in a maintenance setting right after chemotherapy and clinical trials are looking at it in the up-front setting in combination with chemotherapy. That’s a little bit more challenging because of the side effects but we’re also looking at PARP inhibitors for both breast cancer, ovarian cancer and some of the other solid tumours with immunotherapy. So that’s very, very promising and we look forward to the future trials on that. We thank all these courageous patients who are enrolling in these clinical trials so that we can find answers.