ADCs and PARP Inhibitors Are Among 2025’s Practice-Changing Agents in Ovarian Cancer

Deena M. Atieh Graham, MD

Since the December 2014 FDA approval of the PARP inhibitor olaparib (Lynparza) for the treatment of patients with BRCA-mutant advanced ovarian cancer, the respective treatment landscape has seen immense developments, from targeted therapies like PARP inhibitors to antibody-drug conjugates (ADCs), according to Deena M. Atieh Graham, MD.¹

Most recently, the FDA approved the ADC mirvetuximab soravtansine-gynx (Elahere) in March 2024, for the treatment of patients with folate receptor α (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have previously received 1 to 3 systemic therapy regimens.² The approval was based on efficacy data from the phase 3 MIRASOL trial (NCT04209855), which randomly assigned patients 1:1 to receive either intravenous mirvetuximab soravtansine or investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan).

“I think ADCs are here to stay,” Graham said in an interview with OncLive® on World Ovarian Cancer Day, observed annually on May 8. “What we’ve learned in other tumor types, like breast cancer, is that it’s not just about the target.”

During the interview, Graham highlighted the current treatment landscape with practice-changing therapies, treatment selection considerations, mirvetuximab soravtansine’s effect on clinical practice, and challenges and unmet needs that remain in the ovarian cancer space.

Graham is a medical oncologist at the John Theurer Cancer Center at Hackensack Meridian Health in New Jersey.

OncLive: What shifts within the ovarian cancer landscape are leading to better outcomes?

Graham: In terms of the current landscape of ovarian cancer, the majority of what we’re seeing are patients presenting with advanced disease, so stage III or IV disease. Some of the most interesting things are how we approach that. Relatively recent data suggest that neoadjuvant therapy is as good as adjuvant therapy, so we are giving a bit more neoadjuvant chemotherapy. Now that we have those data, it’s important for our patients because it leads to equal outcomes, and we can consider not just aspects of what’s going on with the tumor, but also what’s going on with the patient. If they may not be ready for a major surgery but could get through chemotherapy, it could lead to better outcomes. That’s one thing that’s good. In terms of the other areas that are important, the delivery of maintenance therapy is an evolving area where we are giving bevacizumab [Avastin] as maintenance, typically for patients who are BRCA negative, either somatic or germline, and are homologous recombination deficiency [HRD] negative. The more prevalent use of PARP inhibitors and maintenance has now become the standard of care for patients with BRCA-mutated disease.

What have been the most practice-changing treatments in this space in recent years?

The [use of] PARP inhibitors as maintenance therapy has been one of the most practice-changing [approaches] and that’s very exciting for our patients. I also think the concept of looking at ovarian cancer in a more personalized way, where we’re doing germline and somatic testing on patients and the tumor has led to the use of targeted therapies, which is very important and provides good proof of concept because it tells us that we need to look for better targets. Ultimately, it’s going to lead to better outcomes for patients.

What factors do you consider when selecting a treatment regimen in the first- and second-line setting and beyond?

In terms of first-line therapy and maintenance, germline genetic testing and somatic testing on the tumor [is the process] I typically [choose] for patients in subsequent lines of therapy. We also want to have FRαand HER2 testing. [These days] many [of us] are sending next-generation sequencing on a lot of our patients because other targeted therapies are directed against important driver mutations. Finally, although it’s not the majority of patients with ovarian cancer, testing for Lynch syndrome may be important, particularly in certain types of ovarian cancer, like endometrioid cancers, which would be important in terms of treatment planning.

How has the March 2024 FDA approval of mirvetuximab soravtansine affected clinical practice?

An ADC is made up of 3 aspects: the linker, payload, and monoclonal antibody. To take care of patients with ovarian cancer, we need to know and understand more about the tumor to develop more targeted therapies. [The same is true for] the use of HER2-directed agents.

With these data in the platinum-refractory setting, particularly for [mirvetuximab soravtansine], we’re also awaiting the results of the [phase 3] GLORIOSA study [NCT05445778], which is utilizing this drug in the maintenance setting. This again is developing a targeted maintenance [strategy]. Before, we would have treated everybody with ovarian cancer similarly. Now we’re using personalized medicine more, which is going to be the way of the future.

How do combination regimens currently fit into the treatment paradigm?

Right now, we’re mostly using combination regimens in the maintenance setting, [especially] in BRCA-[mutant] or HRD-positive disease, where we’re using PARP inhibitors and bevacizumab. The data from the 2025 SGO Annual Meeting on Women’s Cancer in March looked at novel combinations of immunotherapy and PARP inhibitors, which is interesting. This is something that is ultimately going to be incorporated into our practice. There are still a lot of questions as to who benefits from that treatment, who may not benefit, and to whom the treatment may be harmful. The full story is yet to come, but utilizing those combinations of immune checkpoint inhibitors, PARP inhibitors, along with chemotherapy and potentially bevacizumab, is on the horizon.

What challenges and unmet needs remain in the field?

Our biggest unmet need is finding out how to identify ovarian cancer sooner, and how to diagnose or prevent it from happening, because most of our patients are still being diagnosed with advanced stage disease—that's a huge unmet need. In certain areas, genetic and genomic testing may not be readily available, and it was previously relevant for detecting cancers in family members. However, now it has a therapeutic benefit for the individual patient, which is an unmet need in some areas that don’t have access [to it].

[We also need more] supportive care for our patients; these are difficult diseases to deal with and lead to a lot of symptoms. Nutritional and psychosocial support for our patients is always an unmet need that may not be spoken about readily, as supportive and [therapeutic] medications are, but it’s key to having patients remain compliant, particularly now that oral agents are being continued for 2 to 3 years as maintenance.

Are there any agents that you’re excited about as they move through development?

In the future personalized approaches [will be more prevalent] for each patient, because it’s going to be the key to identifying which treatments work and minimizing toxicity or exposures to medications that may not work. Also, at SGO, some data were presented looking at WEE1 inhibitors in patients who were platinum refractory, and there are some good signals there. There is also a dual PARP and Wnt inhibitor [that was evaluated] in heavily pretreated patients. [The goal of all this research is to] identify drivers of the disease, so that we can [match patients with an optimal] therapy. That’s something we’re very excited about. We’re [also looking forward to outcomes from the] GLORIOSA study, which is assessing mirvetuximab soravtansine as maintenance.

References

1. Lynparza approved by the US food and drug administration for the treatment of advanced ovarian cancer in patients with germline BRCA-mutations. News release. AstraZeneca. December 19, 2014. Accessed May 7, 2025. https://www.astrazeneca.com/media-centre/press-releases/2014/lynparza-approved-us-fda-brca-mutated-ovarian-cancer-treatment-19122014.html
2. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. March 22, 2024. Accessed May 7, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian