Patient Communication is Key to Delivering Optimal PARP Inhibitor Treatment in Ovarian Cancer

Honest and comprehensive patient-focused discussions during each stage of ovarian cancer treatment should be a part of treatment plans for all patients with ovarian cancer who receive PARP inhibition, according to Laura J. Chambers, DO, who emphasized that additional research is needed to determine the long-term efficacy profile of this class of agents in previously untreated patients.

“PARP inhibitors over the past decade have changed how we treat patients with ovarian cancer,” Chambers said in an interview with OncLive^®. “Twenty years ago, we didn’t have maintenance therapy options, and now we do. That setting is rapidly changing, and the indications [for PARP inhibitors] have evolved, even over the past few years.”

In the interview, Chambers discussed the ways that updated data with niraparib (Zejula) and olaparib (Lynparza) in ovarian cancer have altered clinical practice, potential future research directions that may help clarify the role of PARP inhibitors in platinum chemotherapy resistance, and the importance of upfront communication with patients through every step of their treatment.

Chambers is an assistant pr ofessor in the Division of Gynecologic Oncology at The Ohio State University, as well as an osteopathic physician at The Ohio State University Comprehensive Cancer Center—James, in Columbus.

OncLive: How has the use of PARP inhibitors in ovarian cancer evolved recently, and how have these changes to the treatment paradigm affected your clinical practice?

Chambers: In the United States, 3 PARP inhibitors for patients with ovarian cancer are approved by the FDA. Over the past couple years, the indications [for PARP inhibitors] in the frontline maintenance setting haven’t changed a lot, but in the recurrent setting have. [This is] because of updated data showing concern about overall survival [OS] detriment [with PARP inhibitors] in certain populations of patients. That’s changed how a lot of us use PARP inhibitors.

For patients in the frontline maintenance setting who have undergone chemotherapy and surgery and have had a partial or complete response, the 2 approved PARP inhibitors are olaparib¹ and niraparib.² Olaparib can either be given alone or in combination with bevacizumab [Avastin] for patients who have homologous recombination–deficient [HRD] disease.³ Niraparib is approved for all patients. [In the pivotal phase 3 PRIMA trial (NCT02655016), there was] benefit for progression-free survival [(PFS) with maintenance niraparib vs placebo] in the intention-to-treat, HRD, BRCA-mutant, and homologous recombination–proficient [HRP] populations.²

I rely heavily on genetic and somatic testing results. I refer all patients for genetic testing, I get germline and somatic testing on their tumors, and then I make a lot of decisions [regarding the use of] bevacizumab. Certain patients benefit from bevacizumab maintenance therapy based on [findings from] the phase 3 ICON7 [ISRCTN91273375]⁴ and GOG-218 [NCT00262847]⁵ trials; [those populations include patients with] stage IV disease, ascites, or suboptimal surgery. If I’m going to start a patient on bevacizumab plus chemotherapy and continue [this regimen] as a maintenance therapy option and [I see that] they have HRD disease on somatic test results, I generally will add olaparib to that regimen. If I’m not planning on treating them with bevacizumab, then based upon either their germline or somatic test results, I would choose niraparib based on findings from the PRIMA study, or, if they’re BRCA mutant, I would choose olaparib based on the phase 3 SOLO2 trial [NCT01874353] data.

Could you expand on toxicities, including financial toxicities, that are associated with these agents? How may future investigations address remaining unmet needs for these patients?

Even though we have indications for these medicines, these agents are not always covered by patients’ insurance companies. It’s not uncommon [for PARP inhibitors to cost patients] $2000 a month, which is crazily expensive. Most patients can’t afford that, especially when they have the added burden of maybe being out of work during cancer treatment, [as well as other] financial toxicities of having cancer. That’s an important consideration.

[Regarding adverse effects (AEs) associated with] PARP inhibitors, [these agents can cause] hematologic AEs, especially thrombocytopenia and anemia, as well as gastrointestinal AEs and fatigue. Overall, we do a good job of managing those AEs. However, making sure patients can still have a good quality of life during maintenance therapy is important.

What’s also interesting is when and how PARP inhibitors should be given. Recent data indicating that PARP inhibitors may worsen platinum resistance or make a tumor resistant to platinum are concerning to me because for patients with ovarian cancer, platinum chemotherapy is the most effective treatment at this point. If something is potentially making the tumor become more resistant, that’s concerning for later-line therapy. Understanding PARP inhibitor resistance, platinum chemotherapy resistance, and ways we can potentially reverse that chemoresistance is an area that needs to be studied in the future.

What ongoing PARP inhibitor trials may inform the future use of these agents in patients with ovarian cancer?

We have the OS data from the phase 3 PAOLA-1 trial [NCT02477644], but we’re still waiting on the OS data from the phase 3 ATHENA-MONO [NCT03522246] and PRIMA trials. Those analyses will help guide this [field]. We were excited about PARP inhibitors in the second-line maintenance setting, and then [the phase 3 NOVA trial (NCT01847274)] data showed [a potential] OS detriment [with niraparib vs placebo].⁶ We’re all waiting to see. Hopefully, we don’t see an [OS detriment] in the frontline setting as well. 

What advice do you have for colleagues about discussing PARP inhibitor treatment with patients?

All patients with ovarian cancer should be referred to a genetic counselor, and they should all undergo germline and somatic testing. Having that done up front when they’re first diagnosed is helpful because it informs maintenance therapy decisions. Ultimately, the decision for maintenance therapy has to happen [early]. It can’t happen at the visit for cycle 6 [of induction therapy].

I start talking to patients about [maintenance therapy] when they’re first diagnosed. I talk through their surgery options and their chemotherapy options and let them know that there will likely be maintenance therapy options recommended. That’s important because [patients] always want to know when they’re going to be done, and [we don’t want them to be] surprised that they may have 2 or 3 more years of therapy. That discussion needs to happen early so they can mentally prepare for it.

Patient counseling is also important. From the data with PARP inhibitors, we know that the most substantial benefit is in patients with HRD or BRCA mutations. The indication [for niraparib is in] all patients, and in the all-comer or HRP populations, it’s important to counsel patients that even though there is a PFS benefit [with maintenance niraparib vs placebo], that benefit is approximately 3 to 4 months. 

[PARP inhibitor therapy is potentially] a lot for patients to go through regarding AEs, blood draws, cost, etc. Be honest with patients about the cohort they fall in, what those data look like, the AEs, and that some data have shown that these agents may not be beneficial in later lines. We’re all doing the best we can with the data we have, but it’s important to have frank conversations with patients that are built on at each clinic visit. When we tell patients on their last chemotherapy visit that they’re going to start maintenance therapy now, it’s a lot for them. These are discussions I like to build on over time.

References

1. FDA approves olaparib tablets for maintenance treatment in ovarian cancer. FDA. August 17, 2017. Accessed October 29, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-tablets-maintenance-treatment-ovarian-cancer
2. FDA approves niraparib for first-line maintenance of advanced ovarian cancer. FDA. April 29, 2020. Accessed October 29, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer
3. Lynparza (olaparib) approved by FDA as first-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer. May 8, 2020. Accessed October 29, 2024. https://www.merck.com/news/lynparza-olaparib-approved-by-fda-as-first-line-maintenance-treatment-with-bevacizumab-for-hrd-positive-advanced-ovarian-cancer/
4. Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16(8):928-36. doi:10.1016/S1470-2045(15)00086-8
5. Tewari KS, Burger RA, Enserro D, et al. Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer. J Clin Oncol. 2019;37(26):2317-2328. doi:10.1200/JCO.19.01009
6. Matulonis U, Herrstedt J, Oza A, et al. Final overall survival and long-term safety in the ENGOT-OV16/NOVA phase III trial of niraparib in patients with recurrent ovarian cancer. Gynecol Oncol. 2023;176(suppl 1):S31-S32. doi:10.1016/j.ygyno.2023.06.508