Melissa Hardesty, MD, Details Keys Takeaways From the OVARIO Trial With Niraparib Plus Bevacizumab in Advanced Ovarian Cancer

Adding maintenance niraparib (Zejula) to bevacizumab (Avastin) was associated with delayed disease recurrence in a population of patients with advanced ovarian cancer, according to Melissa Hardesty, MD.

The combination was assessed following frontline platinum-based chemotherapy with bevacizumab as part of the phase 2 OVARIO trial (NCT03326193). The combination resulted in a median progression-free survival (PFS) of 19.6 months and a time to first subsequent therapy of 17.5 months. The time to subsequent second therapy was not reached. Moreover, the 18- and 24-month PFS rates in the overall population were 62% (95% CI, 52%-71%) and 53% (95% CI, 43%-63%), respectively

“This regimen has great efficacy [in] a high-risk group of women. To have no recurrent disease in patients who are getting scans, or labs, regularly is good,” Hardesty stated. “Maintenance therapy is here to stay. Personally for my own practice, when I think about the role of the various agents that we have to treat ovarian cancer, most of us have moved [it in] our brains to more of a chronic disease model. I’m trying to utilize the various therapeutics that I have as long as possible to keep the other things in my toolbox so I have options for patients.”

In an interview with CancerNetwork® during The Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer, Hardesty, a gynecologic-oncologist at Alaska Women’s Cancer Care, discussed the potential synergy between the 2 agents as well as previous findings with the combination.

Could you describe the rationale for assessing niraparib and bevacizumab after frontline chemotherapy in advanced ovarian cancer?

Unfortunately, advanced ovarian cancer is a disease that typically recurs, and we’ve seen a lot of incredible progress with the incorporation of PARP inhibitors, specifically in the mutation-carrier population. With the [phase 3] SOLO-1 trial [NCT01844986], we just saw absolutely incredible results. Most of us are hoping that it’s going to translate to an increased cure fraction. We want that for all of our patients. It’s not something that we’ve seen necessarily with PARP inhibitors as monotherapy. We certainly have seen improvement in that situation, but there are still too many women who are recurring.

The rationale behind the combination is that the preclinical and biological mechanism of action of those 2 agents offer some hope of synergy. We all want to cure these women. We don’t want them to recur because once they do, you’re basically looking at a lifetime of chemotherapy and other therapies. If you can get a home run out of the gate, then that’s a win.

What results have previously been seen from the OVARIO trial?

[In terms of previous findings from the] OVARIO trial, we presented the primary outcome last year which was PFS rate. The updated analysis that we’re presenting at this meeting reported on the parameters that most practicing clinicians are more familiar with [like median] PFS as well as some of the patient-reported outcomes and time to subsequent therapy.

Could you speak to the study’s updated results?

The [median] PFS for all-comers in this trial was 19.6 months. If you look at the comparator arms of other trials [such as] SOLO1 for example—which is an incredibly good prognostic group—it’s good for a couple of reasons. But in general, we as clinicians think of mutation carriers as being the ones who are going to respond the best to treatment because the biology would have you believe that’s the case. But in those women [who] didn’t get any maintenance therapy, the median recurrence after they finished their up-front therapy was 12 months.

Now we have a very high-risk group of patients. Almost half of [these patients] had persistent disease at the end of up-front therapy and none of us as clinicians want keep them permanently on therapy with the [adverse] effects [AEs].

What was seen in terms of new safety findings and patient reported outcomes?

There weren’t any new safety findings. This regimen isn’t easy. The thrombocytopenia is the thing that needs the most awareness. You have to be on top of it and be willing to do dose interruptions and dose reductions; you’re still seeing efficacy with doing that. It takes awareness and diligence with labs. But most of the serious AEs can be avoided. Most clinicians are very comfortable with hypertension as it relates to bevacizumab. This is an agent that we’ve been using for a long time and so that part of it is not very intimidating. It’s more the PARP [AEs that clinicians need to be aware of and adjust to].

If you’re careful, pay attention to labs, and have a very low threshold [for] when you see platelets going down to hold therapy or dose reduce, then you can avoid a lot of the [AEs resulting in] hospital admission which is really what we want. [If] somebody’s platelet count is 70 × 109/L, as long as they’re not doing some ridiculous activity, it really is just a lab number and it doesn’t have any meaningful impact for people. This regimen takes a bit of work, but a median PFS of 19.6 months is worth it.

The most [notable] difference between bevacizumab and PARP inhibitors is where you get your bang for your buck. The the medical community in the United States has been slower to [use] up-front bevacizumab because [many feel that with the] agent you see benefit at various time points duringtreatment and get the same amount of benefit. I don’t think the same is true for PARP inhibition. You get the most bang for your buck earlier on in the disease.

In real medicine, our ability to reliably determine homologous recombination deficiency is moderate. It’s not great. Potentially not offering that therapy to somebody based on those result, [is not something] I’m comfortable with. I think everybody deserves to have the opportunity to have PARP inhibition for advanced ovarian cancer. If they progress through it, you haven’t lost a whole lot.

Reference

Hardesty MM, Krivak T, Wright GS, et al. OVARIO, a phase 2 Study of niraparib + bevacizumab in advanced ovarian cancer following front-line platinum-based chemotherapy with bevacizumab: updated analysis. Presented at: 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022. Phoenix, Arizona.