A comprehensive overview of recent clinical trial data on PARP inhibitors in the first-line maintenance setting in ovarian cancer presented at ASCO 2023.
Ritu Salani, MD, MBA: There were some data presented at SGO [Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in Tampa, Florida,] and here at ASCO [2023 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois,] that…were exploring the space a little further. Some of the abstracts that we’re going to talk about include data that we’re still processing, but let’s start with the effectiveness of PARP inhibitor maintenance and ovarian cancer, looking specifically at BCRA1/2 and the HRD signature in real-world practice. I’d love anybody’s take on what they think about this abstract that was presented by Dr Richardson and company.
Matthew A. Powell, MD: Debra Richardson, MD, FACS, FACOG, was utilizing a tissue bank database that looked across the patients who had a real-world setting. So they received PARP inhibitors, and there [were] groups that didn’t, and [that] was confirmatory for what the [findings from] randomized trials showed us: those patients with BRCA mutation, either germline or tumor, benefited with a very nice hazard ratio. Also, that HRD population seemed to benefit. Both those benefits were seen in progression-free [survival] and hint [at] the overall survival trend as well. So [it’s] further evidence that this is the right thing to do. Our guidelines support this, and now we have real-world data that help support that as well.
Ursula A. Matulonis, MD: It’s important to point out to everyone that once in a while, there is a discussion where you should wait to use the PARP inhibitor in the recurrence setting. That has to be dispelled. This is the standard of care: to add a PARP inhibitor. You’ve seen it in [findings from] phase 3 trial. You’re seeing the benefit in real-world data that Matt just mentioned. So it’s important for clinicians to think about PARP inhibitor use in appropriate patients as [patients receive a] new [diagnosis].
Ritu Salani, MD, MBA: One of your colleagues, Whitney Graybill, MD, MS, presented an abstract on predictors of long-term, progression-free survival in patients treated [with] niraparib from PRIMA. I’m wondering whether you have any takes on that?
Shannon N. Westin, MD, MPH, FACOG: These are important subset analyses to look at to try to tease out and better personalize care for patients. I don’t think there was anything surprising about what they found, which was [that] the biomarkers mattered. The presence of germline somatic mutations was best, HRD next, the bulk of the tumor, how well the surgical outcomes were achieved, those types of things. Some of the nuances are there, but there wasn’t anything that was surprising. But it was more confirmatory of what we already believe.
Ritu Salani, MD, MBA: It’s always nice when real-world practice is confirmed by [study findings] or the [study findings] are confirmed by real-world practice. One of the trials that was presented this time was by Dr Harter and colleagues: the DUO-O study [NCT03737643]. So durvalumab with paclitaxel, carboplatin, and bevacizumab followed by maintenance durvalumab, bevacizumab, and olaparib in patients with newly diagnosed advanced ovarian cancer without a tumor BRCA1 or [BRCA2] mutation. This was a randomized, placebo-controlled, phase 3 trial. There was a lot of excitement about this. We had seen a press release that this was a positive study [result], and I’d love to hear your takes now that we’ve seen the actual abstract presented.
Ursula A. Matulonis, MD: All these up-front phase 3 trials take so much work, effort, and time. Patients are so generous to participate in the trials, and the investigators are so connected with the trials. A trial like this is an iterative process, and we need to see a succession of results. The other issue is that when trials are developed, standard of care changes when that trial is being executed, launched, and run. We talked about in PAOLA-1 [that] olaparib-bevacizumab is now a standard-of-care arm for patients who receive bevacizumab in the HRD setting and in the BRCA-mutated setting. That arm does not exist in this trial, and it’s not an omission, but it’s an important deficiency of this study. There are no overall survival data, which are critical for PARP inhibitor trials now.
Bhavana Pothuri, MD: They didn’t have that standard right when they designed this trial, which is a good thing, because that means we continue to make progress in the field. The other thing is that the HRP group was just a subset. It would’ve been very nice if that was analytic, because that’s the subset that we want to benefit the most and where they did see benefit in terms of their hazard ratio, but unfortunately [that] was not an analytic subgroup.
Shannon N. Westin, MD, MPH, FACOG: The bottom line is the study [result] was written as positive. As the study was written and designed, it was a positive trial [result]. The triplet provided an improvement in progression-free survival and over the control arm in both the HRD population [with] non–BRCA-mutant [disease] and in the intention-to-treat population. As Bhavana just said, if we knew then what we know now, we would’ve really driven this trial to be analytic for the population who needs the most benefit, which is that homologous recombination deficiency group [with] negative test [results]. It’s intriguing what we see in that arm. It seems to be numerically improving over [results from] PAOLA-1, which is part bevacizumab, but we can’t say that for sure. But it is intriguing.
Matthew A. Powell, MD: It’s hard to know what that individual contribution of the checkpoint inhibitor is adding to this population. Again, with the financial toxicity [and] the other things, I’m not quite ready to jump to that conclusion that it’s ready for prime time. Obviously, [it’s] a fantastic study, and I think Dr Harter mentioned about 200 patients were enrolled in the trial by the time the PAOLA-1 data came out. They did consider adding in another arm, but it [was] not feasible given the way the study was run.
Bhavana Pothuri, MD: If you looked at that HRP subset, the hazard ratio is the same as that for PRIMA, 0.68, and very similar in terms of progression-free survival benefit. So it makes you wonder.
Ursula A. Matulonis, MD: We’re also learning…about the continued use of testing IO [immuno-oncology] in different settings. In the HRP group, when durvalumab is added, the numerical median PFS drops a little. There’s also been recent publication from IMagyn050 in CCR [Clinical Cancer Research] that the HRD status is a negative trial [result], but it wasn’t as if the patients [with] HRP [disease] have an improved outcome with the addition of an immunotherapy. So it really depends on the interaction of the PARP inhibitor with the IO, and we’re going to have a hard time teasing that out in this trial.
Matthew A. Powell, MD: The good news is we have lots of these study [data] maturing. We’re going to have a lot to talk about.
Ritu Salani, MD, MBA: It makes it a little hard to interpret the data, and I don’t think it’s going to change practice, but we’ll see as more data come out.
Transcript edited for clarity.