Ocular Toxicity Management and Early FRα Testing Are Key to Maximizing Efficacy of Mirvetuximab Soravtansine in Ovarian Cancer

Integrating new therapies with appropriate therapeutic sequencing and personalized care into clinical practice for ovarian cancer remains critical for improving patient survival and quality of life (QOL), according to Ritu Salani, MD, who added that for one agent in particular, mirvetuximab soravtansine-gynx (Elahere), optimal integration requires early testing for folate receptor alpha (FRα) expression and collaboration with specialists to manage ocular toxicities.

The FDA granted accelerated approval to mirvetuximab soravtansine in 2022 for patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic treatment regimens.1 The regulatory decision was supported by findings from the phase 3 SORAYA trial (NCT04296890), and confirmed by results from the phase 3 MIRASOL trial (NCT04209855), which showed an overall survival (OS) benefit with mirvetuximab soravtansine vs investigator’s choice of chemotherapy.2

“This is a time of great exploration in ovarian cancer. We’re seeing a lot of new antibody-drug conjugates [ADCs] emerging in the space, and understanding which ADC to use, when to use it, and how to sequence them if that’s even possible, is important,” said Salani, who is the director of Gynecologic Oncology at UCLA. “It’s important we test patients for [FRα expression], as [mirvetuximab soravtansine] is FDA approved, but it’s also important to remind ourselves that there are opportunities to improve the care of these patients [in other ways] as well.”

In an interview with OncLive®, Salani discussed the importance of testing for FRα expression in patients with ovarian cancer to guide the use of mirvetuximab soravtansine, and emphasized the need for specialist involvement, particularly for the management of ocular toxicities. Salani also touched on the evolving role of mirvetuximab soravtansine in ovarian cancer, the challenges with treatment selection in platinum-resistant disease, and the importance of not only improving survival but attempting to improve cure rates through ongoing research.

OncLive: Given the current FDA approval for mirvetuximab, what point do you recommend patients with ovarian cancer be tested for FRα expression?

Salani: The introduction of mirvetuximab soravtansine into the clinical setting with FDA approval has changed the landscape for ovarian cancer. We often perform next-generation sequencing at the time of diagnosis for patients with ovarian cancer. At that time, many of these commercial assays [can be performed], [including] immunohistochemistry testing. This allows us to obtain the folate receptor status at the time of diagnosis, which is a nice piece of information to have for potential future use.

Why is it important to consult eye specialists when approaching the management of mirvetuximab soravtansine–related ocular toxicities?

We see the onset of eye toxicities with not only mirvetuximab soravtansine but with some other ADCs, and they can vary between ADCs. Patients may have blurry vision, photophobia or light sensitivity, eye pain, and occasionally floaters. [Therefore], seeing an eye specialist is important to maintain optimal visual acuity and make sure that the patient’s eye care is being properly assessed or that eye drops are being [administered to] mitigate any toxicities. It’s nice to work with an ophthalmologist, optometrist, or eye specialist who can help advise patients on the role of eye drops. As we’re using [mirvetuximab soravtansine] more and more, we’re starting to see some newer adverse effects [AEs], especially like cataracts. [These] may not be related to the drug, but the eye drops, so understanding the nuances of how this drug may affect the eyes and vision is important.

It is fairly easy to ascertain if the patients have symptoms. I’m hopeful that, at some point, we may be able to decrease the role of the eye specialist. However, at this point, the visual acuity fields are important, and seeing an ophthalmologist or optometrist is advised.

Aside from ocular toxicities, do any other AEs associated with mirvetuximab soravtansine require specialist intervention?

Some of the other AEs that we see with mirvetuximab soravtansine may be less common or less extreme, but they are important to recognize. We’re familiar with [managing] cytopenias, and we also see neuropathy from the use of mirvetuximab soravtansine. Pneumonitis may also occur, and it’s not uncommon that we’ll partner with specialists like a pulmonologist to help manage some of the AEs that patients may be experiencing. For anything that’s out of our territory of familiarity, partnering with other medical specialties is important to optimize patient care and safety, [which] allows them to stay on an effective medication as long as they can.

How might improper AE management affect the efficacy of mirvetuximab soravtansine among responders?

When patients report symptoms and they’re having a response, [we worry that] they may minimize their symptoms because they’re worried about dose reductions, dose delays, or potentially even discontinuation of the drug. However, some of these AEs may be irreversible, so it’s important to emphasize to patients how important it is to accurately report symptoms, especially those that aren’t measurable, such as neuropathy and certain ocular toxicities. [If unaddressed, these AEs] can cause long-term damage to the patient’s QOL or functional status. [Dose] reductions or even holding the dose may be a very appropriate intervention that minimizes toxicities without a loss of efficacy. Discontinuation of the drug is never something that we like to do, but if it’s in the patient’s best interest, it’s an important part of cancer therapy.

How was platinum resistance defined in the pivotal MIRASOL trial? Is it the same definition you adhere to when considering patients for treatment with mirvetuximab soravtansine?

For this study, patients were required to have platinum-resistant ovarian cancer, which was defined as no progression within 3 to 6 months of their last platinum-containing regimen. This is a common definition. We do have platinum-refractory patients who progress on or right after the completion of platinum, and those patients have a poor prognosis. Their disease biology is by far less responsive to second- or next-line chemotherapies. This is a typical definition, and it still represents a very challenging group to treat because of their disease biology. Therefore, the fact that we saw a positive signal with this drug [for such patients] is very impactful.

Have survival outcomes and response rates been maintained in subsequent analyses of MIRASOL? Do these appear to correspond with outcomes in clinical practice?

We’ve continued to see secondary or ancillary studies from the MIRASOL trial, and the data have continued to show the benefit of mirvetuximab soravtansine in this setting with [regard to] progression-free survival, OS, and QOL. Anecdotally, in my patient practice, I’m also seeing responses that are comparable to what was reported. Our real-life experience really does [seem to] mirror the study results.

How does mirvetuximab soravtansine fit into the treatment landscape for ovarian cancer, and how might future research help optimize its use and sequencing with other therapies?

Mirvetuximab soravtansine plays a significant role for patients with high FRα-expression in their tumor. [However], we need to understand what to do for patients who may have a more dynamic test result, [e.g.] a result that is negative at one point but positive at another, or patients who have heterogeneity in their testing results.

There are lots of clinical trials in development [in ovarian cancer], and finding the right one for our patients is important. Many of them may require certain therapies to be delivered beforehand, and understanding [the optimal] sequencing is going to be important for these patients. We’re improving survival, and that’s a good thing, but we only have success when we develop cures.

References

1. ImmunoGen announces FDA accelerated approval of Elahere (mirvetuximab soravtansine-gynx) for the treatment of platinum-resistant ovarian cancer. News release. ImmunoGen Inc. November 14, 2022. Accessed December 17, 2024. https://news.abbvie.com/2022-11-14-ImmunoGen-Announces-FDA-Accelerated-Approval-of-ELAHERE-TM-mirvetuximab-soravtansine-gynx-for-the-Treatment-of-Platinum-Resistant-Ovarian-Cancer
2. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. March 22, 2024. Accessed December 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian