Clinical insights on adverse effects seen with PARP inhibitors in the treatment of patients with ovarian cancer.
Case: A 49-Year-Old Woman with BRCA-WT Ovarian Cancer
Chad A. Hamilton, MD: When we talk about PARP inhibitors, the efficacy data has really been the headline that screams at you. These are practice-changing studies that we’ve seen. But it’s also important to discuss the toxicities and adverse events that are associated with PARP inhibitors and making patients aware of what to expect. I think my experience is the adverse effects I’ve seen are really the same ones that are most commonly reported in the studies. I usually think about them in terms of hematologic vs nonhematologic adverse events. Of course, we’re monitoring closely for anemia, thrombocytopenia, and neutropenia with frequent lab tests. That’s usually a baseline test for blood counts. For niraparib, we checked weekly for the first month and then monthly thereafter, and every 2 to 3 months after year 1. For olaparib, we’re checking a baseline and then following that monthly thereafter.
Some of the more common nonhematologic toxicities I see are usually GI [gastrointestinal] related, like nausea, constipation, and perhaps diarrhea or abdominal pain. Fatigue is pretty common, and that can be a tough one to sort out regarding how much is drug related vs multifactorial. And I’ve certainly seen a handful of patients with headaches and joint pain and some of those less common adverse effects. I generally don’t try to parse out too much adverse effects from one PARP vs another because most of the adverse effects are class effects of the PARP inhibitors. Of course, if you’re putting someone on a [phase 3] PAOLA-1 [trial (NCT02477644)] regimen, then you have to factor in the bevacizumab-related adverse effects in addition, like hypertension or proteinuria.
As far as unusual adverse effects or toxicities that I didn’t anticipate, you do have to keep your eye open for those things that occur in 10% or 5% or less, because patients will come in with those things, and it’s easy to write them off as from other sources. I’ve had a couple of patients with persistent nasopharyngitis that’s reported, but it’s rare. [I’ve had] patients with change in taste. I’ve had some with palpitations and shortness of breath, which aren’t really that common, but upon dose interruptions, a pretty profound improvement in symptoms certainly made me aware that it was likely the drug that was causing these adverse effects. I’ve had 1 patient that comes to mind with pretty profound pancytopenia that was several months into therapy. Usually, these cytopenias occur early on in treatment if they occur, so it was fairly anxiety provoking when it occurred. It ultimately did resolve and fortunately didn’t evolve into MDS [myelodysplastic syndrome] or AML [acute myeloid leukemia], but that’s always in the back of our mind and certainly something I think is important to discuss that possibility with patients. It can be very scary, but then you really have to contrast that with the, like we talked about, upwards of 80% to 85% chance of recurrence from their cancer with standard approaches. It’s really balancing that risk vs potential benefit.
I really haven’t noticed a big difference in adverse effects of the PARP inhibitors as they migrated into the frontline setting vs when we initially started treating patients after recurrence. Sometimes patients are a little bit more beat up in the recurrent setting. The PARP inhibitors actually may be a little bit better tolerated in this frontline setting. But that’s largely anecdotal. And we haven’t seen a big difference in adverse effects signals from the frontline from some of the earlier data from later-line trials.
Transcript is AI-generated and edited for clarity and readability.