Floor J. Backes, MD, discusses subtle differences among PARP inhibitors that can help determine their optimal use in advanced ovarian cancer.
Floor J. Backes, MD
PARP inhibitors, with proper patient selection, are as tolerable as they are effective, according to Floor J. Backes, MD. These agents are now being explored in combination to further improve outcomes for patients with advanced ovarian cancer.
“Should we combine PARP inhibitors with antiangiogenic agents, immunotherapy, or PI3K inhibitors? We’ll have to tease out when to prescribe which combination; that is going to be really important for us moving forward,” said Backes.
In an interview during the 2019 OncLive® State of the Science Summit™ on Ovarian Cancer, Backes, associate professor, Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center—James, discussed subtle differences among PARP inhibitors that can help determine their optimal use in advanced ovarian cancer.
OncLive: Could you discuss the different toxicity profiles of PARP inhibitors?
Backes: All of the PARP inhibitors have pretty similar rates of fatigue and severe nausea. The biggest differences are the hematologic adverse events (AEs). Anemia, thrombocytopenia, and neutropenia are more common with niraparib (Zejula). On the other hand, niraparib is given once daily, which would be convenient for patients who can't remember to take their pill multiple times a day. Niraparib can increase your blood pressure, so I try to stay away from that agent in patients who have problems managing their blood pressure. Rucaparib (Rubraca) can raise your cholesterol, so I may try to avoid it in patients who already have high cholesterol.
Could you discuss the quality of life (QoL) data seen with PARP inhibitors?
We don't have QoL data with the up-front studies, but we do have those data in the recurrent setting. The NOVA trial showed that patients were able to maintain their QoL on niraparib. Nausea was a little bit worse in the beginning, but then leveled off. Overall, we saw similar QoL data with olaparib (Lynparza). Investigators also did a quality-adjusted progression-free survival analysis and saw a difference [versus placebo] there as well.
Do you take into account financial toxicity when deciding which PARP inhibitor to prescribe?
Fortunately, insurance has been better at covering these treatments. However, the copay per insurance can vary greatly. Some patients have a $0 copay, while others may have a $900 to $1000 copay per month; that adds up quickly. It's nice that there are copay and assistance programs, but not everybody qualifies for them. If the patient is going to experience financial toxicity from treatment, we have to consider what the added benefit is. All the PARP inhibitors are pretty similar in price, so it depends on physician and patient discussions. Sometimes patients won't tell you that they're struggling to pay their bills every month.
Should additional QoL studies be done with PARP inhibitors?
It will be interesting to see QoL studies for patients receiving PARP inhibitors as frontline maintenance therapy. It will be interesting to see what their QoL is after being on these drugs long term when they are doing well.
What are some remaining questions with PARP inhibitors in ovarian cancer?
We need to figure out who the ideal population is to give these agents to. Who should we expose [to PARP inhibitors], and [for whom] should we bring them into the frontline setting? Additionally, are there other patients who should receive PARP inhibitors, not just in the first- and second-line settings, but also in the recurrent setting? How do we decide which drug to combine these agents with? [In the recurrent setting], it seems like a combination regimen is better.
Are there any concerns for added toxicity with these combination regimens?
Certainly, every agent comes with a whole different set of toxicities. Yes, you have 2 different [safety profiles]; however, if you can offset [those toxicities] with a higher [risk]-benefit ratio, it may be acceptable. We will need to learn how to manage [AEs] and ensure that we give the drugs at the appropriate doses.