Gynecologic Oncologists Highlight Ongoing Areas of Exploration Throughout the Treatment Armamentarium

In gynecologic oncology, there are ongoing studies aiming to address unmet needs in ovarian cancer by providing further options to patients through novel therapies, according to Michael P. Stany, MD, who added that additional questions remain regarding the evolving role of immunotherapy in advanced endometrial cancer.

“The mindset for [the treatment of] ovarian cancer [is] having some sort of maintenance [treatment]—it seems like approximately half of our patients with BRCA-positive or HRD-positive disease are candidates for PARP inhibitors and that’s great,” Stany said in an interview with OncLive® following a State of the Science Summit™ (SOSS) on gynecologic cancer, which he chaired. “It is that pool of patients who are HRD-negative that we’re lacking good options for. Hopefully, [as ongoing trials progress], there will be other things that pop up as suitable maintenance for those patients.”

Stany highlighted that notable phase 3 trials in ovarian cancer evaluating novel agents include the FIRST study (NCT03602859) of platinum-based therapy with dostarlimab (Jemperli) plus niraparib (Zejula); the DUO-O study (NCT03737643) of durvalumab (Imfinzi) in combination with chemotherapy and bevacizumab (Avastin), followed by maintenance durvalumab, bevacizumab and olaparib (Lynparza); and the ATHENA study (NCT03522246) of rucaparib (Rubraca) and nivolumab (Opdivo).

In the interview, Stany, a gynecologic oncologist at Ascension Medical Group, Ascension Saint Thomas, in Nashville, Tennessee, discussed his colleagues’ key takeaways from the SOSS event, highlighting the optimization of PARP inhibitors in the upfront maintenance setting of ovarian cancer, the benefit of novel targets and immunotherapy combinations, and the role of immunotherapy in the treatment of advanced endometrial cancer.

OncLive: You gave a case presentation on the use of PARP inhibitors in ovarian cancer and colleagues highlighted navigating the role of PARP inhibitors. What were key takeaways from these discussions?

Stany: Regarding the case presentation, I spoke on the most common type of patients who present with ovarian cancer, focusing on maintenance options with PARP inhibition, looking at the testing formats that people use to determine homologous recombination deficient [HRD] and BRCA status afterwards. This was then followed by the nuances of what goes into PARP treatment afterwards.

[When determining a maintenance PARP inhibitor] there are several [factors to consider], specifically though, patient tolerability. This includes what they’ve gone through with [given] chemotherapy, as well as convenience—for example, [if the agent is given] once a day vs twice a day for some of the PARP inhibitors. These are the main [considerations].

PARP inhibitors are mainly being used upfront in the maintenance setting now in newly diagnosed disease, not with the later lines. [Regarding potential for these agents for those without BRCA mutations],BRCA-negative, but HRD-positive [disease] falls into that same category. With the phase 3 PRIMA study [NCT02655016] looking at all comers, the data for that a little bit on the weaker side.

What are investigations seeking to bring other agents to the ovarian cancer treatment paradigm as discussed by Mali Schneiter, DO, MBA, of Vanderbilt Health?

The FIRST study looked at the addition of immunotherapy, the DUO-O trial also looked at this [combination approach], and the ATHENA trial [did as well]. There are several trials looking at the addition of immunotherapy in the upfront setting, which is exciting, [and] it seems like with other cancer types there have been positive results as well as some big improvements. Therefore, the other big question mark in ovarian cancer is immunotherapies ultimate role in upfront treatment.

Aaron Nizam, MD, of TriStar Centennial Medical Center, discussed immuno-oncology–based therapies for advanced endometrial cancer. How has immunotherapy changed this treatment paradigm, particularly in the first-line setting?

[We have information] in the upfront setting, about the tumor specifics, things that make the patient and subsequently their tumor qualify for immunotherapy. Microsatellite instability-high, PD-L1, lynch syndrome, and IHC testing are all [factors of consideration] to see if the patient would benefit from immunotherapy. For anybody with metastatic cancer, we want to know these statuses to see if we would add on immuno-oncologic treatments to their adjuvant carboplatin/paclitaxel treatment.

What research is ongoing at your institution?

For ovarian cancer, investigators are looking to the folate receptor treatments earlier. In the platinum-sensitive setting, right now, it’s only authorized for platinum resistance. For endometrial cancer, for serous disease, investigators are looking at WEE1 inhibitors such as ZN-c3.There are a few [agents] that are in the phase 3 [clinical trial] settings for platinum-resistant disease, which is the next step for figuring out additional agents that can be used.