Personalized Medicine Enhances the Ovarian Cancer Treatment Landscape

Eirwen M. Miller, MD

Though the backbone of carboplatin and paclitaxel remains a standard of care for patients with ovarian cancer, the field is seeing a significant shift towards incorporating maintenance therapies like bevacizumab (Avastin) and poly-ADP ribose polymerase (PARP) inhibitors.

This shift reflects an approach utilizing personalized medicine. With the addition of maintenance therapies, experts can better tailor treatments based on individual patient factors and disease characteristics.

Research continues to explore and refine these treatments and identify new options for patients with ovarian cancer. In addition, mirvetuximab soravtansine (Elahere) has made significant strides in the ovarian cancer space. In November 2022, the FDA granted accelerated approval to mirvetuximab for patients with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer who have been previously treated with 1 to 3 prior systemic treatments.

The agent is now being further evaluated in the phase 3 MIRASOL trial (NCT04209855), and data has already shown improvements in progression-free survival, objective response rates, and overall survival, according to findings from 2 subset analyses of the trial.

In an interview with Targeted Oncology, Eirwen M. Miller, MD, gynecologic oncologist at Allegheny Health Network, discussed the dynamic landscape of ovarian cancer treatment, highlighting advancing upfront therapy, preventing recurrences, and new options for patients.

Targeted Oncology: What does the ovarian cancer treatment landscape currently look like?

Miller: When we're thinking about ovarian cancer, we are thinking about how we make progress in upfront therapy. How do we prevent recurrences? How do we get to use the word “cure” in ovarian cancer? We know that recurrence rates are high for patients that are diagnosed at an advanced stage. When we think about the patients that recur, [we subdivide] them into a population of patients that would benefit from additional platinum based chemotherapy and patients where platinum based chemotherapy is not an option for them.

The landscape is huge in upfront ovarian cancer. We're still using a backbone of carboplatin and paclitaxel. I think we've moved into an era where the large majority of patients are receiving maintenance therapy, whether that's bevacizumab or a PARP inhibitor or the combination. There are still some roles for active surveillance, though I think that's really becoming the minority of patients with the FDA approval of PARP inhibitors for all patients following platinum-based chemotherapy for advanced ovarian cancer.

I think where we've seen the most significant advances in the most recent years is probably in the platinum-resistance space. We've had some rapid developments of antibody-drug conjugates with recent FDA approval of mirvetuximab with the phase 3 trial MIRASOL demonstrating progression-free and overall survival benefit with mirvetuximab when compared with investigators' choice of chemotherapy. When we're talking about overall survival benefit in ovarian cancer, these patients have a long-term chronic disease. The ability to demonstrate an overall survival benefit in clinical trials is really difficult, and almost unheard of in recent ovarian cancer clinical trials. So, this is exciting data coming out of this phase 3 trial in the platinum-resistance space, [and] that's certainly going to change our standard of care. It's resulted in new FDA approvals for platinum resistant disease.

What drugs do you think oncologists should pay attention to?

[As for] drugs in early phase trials, we have had a relative gap in new drug developments in the platinum-resistance space. In ovarian cancer, when we're looking at drug development, they're typically introduced in the platinum-resistance space before being advanced into the platinum-sensitive and ultimately the upfront setting. We've not had a lot of opportunities for clinical trials in the platinum-resistance space in the last 1 to 2 years. A lot of the clinical trials that preceded that, largely with the exception of MIRASOL, ended up being negative clinical trials and [those] will not result in FDA approvals.

We have a couple ongoing clinical trials, largely with novel combinations of medications and not necessarily new drug development. I think that we feel largely like we're at a drawing board right now looking for some new opportunities for improvement, but also really excited by some of the improvements that we've seen in the most recently published data.

Looking forward in this space, what do you hope to see coming out of research?

With the addition of PARP inhibitors to the ovarian cancer landscape, we have found a nice target for patients that have homologous recombination-deficient [HRD] tumors. Where I'd really like to see our science go is trying to evaluate an appropriate drug regimen to move the science forward for patients that have homologous recombination-proficient tumors. We're looking and hoping to have some results from some phase 3 clinical trials in the upfront setting, looking at combinations of maintenance therapy, immunotherapy, with PARP inhibitors. Potentially, also with bevacizumab.

We had the results of DUO-O [NCT03737643] presented at [the 2023 American Society of Clinical Oncology Annual Meeting] that showed modest progression-free survival benefits in a homologous recombination-deficient population. As we're looking forward into this landscape, we've made astronomical progress in those HRD patients, but what can we do to portend survival benefits for the patients that are homologous recombination deficient, and how can we put drug combinations together to target those patients?

What is important to note about this disease state and to know when keeping up with the latest research?

In this space, it is highlighting mirvetuximab and MIRASOL. I think that provider education about [adverse] effects from a new drug class, the antibody drug conjugates [is important]. Specifically with MIRASOL, there's some new ocular toxicities that we're seeing and educating providers about recognizing and treating those ocular toxicities is needed. This relatively uncomfortable toxicity profile doesn't preclude getting the drugs to patients because we know the drug is effective.

We at AHN have developed a relationship with our ophthalmologists and our optometrists. It does not have to be an ophthalmologist. It is any eye care professional that can evaluate our patients. We've developed a nice relationship with our eye care professionals, and educated them about the [adverse] effects of this drug in the mitigation strategies so that we're able to get drugs to patients without provider discomfort about the [adverse] effect profile. I think that's important as these new drugs come to market that we're doing what we can to educate, and that not being the barrier to patient care.

REFERENCE

Moore KN, Angelergues, Konecny GE, et al. Phase III MIRASOL (GOG 3045/ENGOT-ov55) study: Initial report of mirvetuximabsoravtansine vs. investigator's choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. J Clin Oncol. 2023;41(suppl 7):LBA5507. doi: 10.1200/JCO.2023.41.17_suppl.LBA5507