Ovarian Cancer Research Outlines the Role of ADCs, PARP Inhibitors, and Surgery

Hope Cottrill, MD

As the ovarian cancer treatment armamentarium expands to include an array of targeted therapies, PARP inhibitors, and antibody-drug conjugates (ADCs), individualized approaches to treatment decisions and adverse effect (AE) management are crucial, according to Hope Cottrill, MD.

“A lot of oncologists and gynecologic oncologists nationwide are looking at the pros and cons of using a single-agent PARP inhibitor vs pembrolizumab [Keytruda] combined with a PARP inhibitor, [using data from] the [phase 3] SOLO-1 [NCT01844986] and PAOLA-1 [NCT02477644] trials,” Cottrill said in an interview with OncLive® following a State of the Science Summit (SOSS) on gynecologic oncology, which she chaired.

Long-term follow-up data from SOLO-1 demonstrated that patients with newly diagnosed, BRCA-mutant ovarian cancer who received olaparib (Lynparza; n = 260) achieved a 7-year overall survival (OS) rate of 67.0% compared with 46.5% for those who received placebo (n = 131). The median OS was not reached vs 75.2 months, respectively (HR 0.55; 95% CI, 0.40-0.76; P = .0004).¹

The PAOLA-1 trial investigated olaparib plus bevacizumab (Avastin) vs placebo plus bevacizumab in patients with newly diagnosed advanced ovarian cancer who achieved clinical response after frontline platinum-based chemotherapy plus bevacizumab.² Patients in the olaparib arm experienced a median OS of 56.5 months vs 51.6 months in the placebo arm (HR, 0.92; 95% CI, 0.76-1.12; P = .4118).

In the interview, Cottrill highlighted key points that were presented at the SOSS meeting, including the role of bevacizumab plus PARP inhibitors in ovarian cancer management, how to manage AEs associated with ADCs, and ongoing research in ovarian cancer risk reduction.

Cottrill is a gynecologic oncologist at Baptist Health Medical Group in Lexington, Kentucky.

OncLive: Based on presentations by David Schweer, MD, Tricia I. Fredricks, MD, and Lauren A. Baldwin, MD, of the University of Kentucky Markey Cancer Center in Lexington, how may clinical trials elucidate the feasibility of combining PARP inhibitors with targeted therapy for patients with ovarian cancer?

Cottrill: [Dr Baldwin discussed] clinical parameters that drove her decision-making process. With the long-term OS data coming out from SOLO-1, do [patients] get additional benefit from the addition of bevacizumab, like with the PAOLA-1 regimen? [Many oncologists] nationwide are on the fence. Some are continuing the bevacizumab if they have already initiated that treatment and later found out the patient was BRCA positive. Others are just [using] a PARP inhibitor. In Dr Baldwin’s presentation, [she discussed how if a patient] was presenting with clinical findings of high-volume ascites and pleural effusions, she was more likely to use bevacizumab, [regardless of] whether they were BRCA positive. She used a variety of clinical data in making that decision.

Regarding the presentation by Dr Baldwin and L. MacKenzie Harbin, MD, of the University of Kentucky Markey Cancer Center, about ADCs and future directions in ovarian cancer treatment, how has mirvetuximab soravtansine-gynx (Elahere) broadened the treatment paradigm for patients with platinum-resistant disease?

[Drs Baldwin and Harbin] talked about mirvetuximab soravtansine, [highlighting] the data and clinical experiences they’ve had [with this agent]; my experiences have been in line with what they [spoke about]. There was an initial problem [with eye toxicities] with other ADCs. Now that we have more experience and our ophthalmologic colleagues are more on board with seeing these patients on regular schedules and [are being reimbursed], so they get paid appropriately for doing that work, we’ve not had the same challenges [scheduling] ophthalmologic follow-ups [for patients receiving mirvetuximab soravtansine] that we initially had with some other ADCs. Monitoring the toxicities carefully [is key].

The [disease subset] that mirvetuximab soravtansine targets, platinum-resistant ovarian cancer, has limited treatment options. It’s nice to be able to give them [an agent] that [is associated with] a median progression-free survival that’s meaningful and toxicities that are well managed, as opposed to chemotherapy options, because a lot of these patients are heavily pretreated and don’t have a lot of reserve left regarding systemic chemotherapy.

What gynecologic oncology clinical trials are ongoing at Baptist Health Medical Group Gynecologic Oncology?

We have the ROCC trial [NCT04831580] that I’m finally going to get a patient on that investigates laparoscopic surgery for patients with early cervical cancer. [Laparoscopic surgery in this population] has fallen out of favor because of a large international trial that showed inferior outcomes with a laparoscopic approach vs radical hysterectomy for early cervical cancer.

We have another surgical trial [NCT04251052] open that evaluates the removal of fallopian tubes for risk reduction in BRCA-positive patients vs the removal of fallopian tubes and ovaries in these patients. That is an intellectual question that needs to be answered because other data support leaving ovaries in until the age of 55 years. Otherwise, there’s a decreased longevity [of life]. We are balancing the risk of getting ovarian cancer, which nobody wants to get if it’s preventable, with the risk of premature death with the removal of ovaries before [the age of 55 years]. [That trial may] take a long time to accrue patients too.

What is the value of events such as this SOSS?

For us, this was a unique event, because although a lot of the other presenters are my colleagues, they’re not people I work with on a day-to-day basis, so I didn’t have a good understanding about their approach to caring for their patients. This was a nice event in that way that I got to understand perspectives of colleagues in the field who practice in the same area. Some practice patterns tend to be regional, but this way, I had a better understanding about what the people who are in practice up the street do.

References

1. DiSilvestro P, Banerjee S, Colombo N, et al. Overall survival with maintenance olaparib at a 7-year follow-up in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation: the SOLO1/GOG 3004 trial. J Clin Oncol. 2023;41(3):609-617. doi:10.1200/JCO.22.01549
2. Ray-Coquard I, Leary A, Pignata S, et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023;34(8):681-692. doi:10.1016/j.annonc.2023.05.005