Multidisciplinary Collaboration Is Crucial in Managing Ocular Toxicities of Mirvetuximab Soravtansine in Gynecologic Tumors

The FRα-directed antibody and microtubule inhibitor conjugate mirvetuximab soravtansine-gynx (Elahere) has provided an additional treatment option for patients with pretreated gynecologic malignancies but special care and coordination with a multidisciplinary team is needed to manage the ocular toxicities and other adverse effects (AEs) that can often accompany treatment with the agent, according to Rebecca Arend, MD, and Kathryn Lyle, CRNP.

“In the gynecologic oncology and oncology space in general, we now have multiple drugs, not just mirvetuximab soravtansine, where there are some concerns for ocular toxicity management with patients,” Lyle said. “When we first started [using mirvetuximab soravtansine], it was [seen as] a new AE and it made a lot of individuals nervous. But now we’ve had a couple of years under our belt managing multiple different agents that also have some of those ocular toxicities. Change can be difficult, but at this point there should be the resources, individuals who you can contact, and others whom you can refer to if you’re not comfortable [in managing these toxicities].”

In November 2022, the FDA granted accelerated approval to mirvetuximab soravtansine for the treatment of adult 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 data from the phase 3 SORAYA trial (NCT04296890), which demonstrated that patients who received the agent (n = 106) achieved a confirmed investigator-assessed overall response rate of 31.7% (95% CI, 22.9%-41.6%) and a median duration of response of 6.9 months (95% CI, 5.6-9.7).

In March 2024, the FDA granted full approval to mirvetuximab soravtansine in the same patient population as the 2022 indication.2 The updated indication was based on findings from the phase 3 MIRASOL trial (NCT04209855), which showed that patients who were treated with mirvetuximab soravtansine achieved a median overall survival of 16.5 months (95% CI, 14.5-24.6) vs 12.7 months (95% CI, 10.9-14.4) among those who received chemotherapy (HR, 0.67; 95% CI, 0.50-0.88; P = .0046). The median progression-free survival was 5.6 months (95% CI, 4.3-5.9) vs 4.0 months (95% CI, 2.9-4.5), respectively (HR, 0.65; 95% CI, 0.52-0.81; P < .0001).

In an interview with OncLive®, Arend, an associate professor of gynecology oncology within the Department of Obstetrics and Gynecology at the University of Alabama at Birmingham, as well as a scientist and coleader of the Experimental Therapeutics Program at the O’Neal Comprehensive Cancer Center, and Lyle, a nurse practitioner in the Department of Gynecologic Oncology at the University of Alabama at Birmingham, discussed the importance of working with specialists to manage ocular toxicities related to mirvetuximab soravtansine and other AEs of interest with the agent.

OncLive: What is the importance of FRα testing in patients for whom you are considering treatment with mirvetuximab soravtansine?

Arend: Several years ago, we implemented somatic testing at the same time [as germline testing]. In our joint oncology practice we preemptively implemented a lot of tumor testing at the time of diagnosis.

When mirvetuximab soravtansine became approved in the platinum-resistant setting, we also had experiences with clinical trials in the platinum-sensitive setting, and we now have an upfront, investigator-initiated trial utilizing it. Due to all of that, it became part of our routine testing for every patient with ovarian cancer. We counsel them that we will test for anything that could be an inherited mutation [as well as] certain things on the tumor, some of which are based on the DNA of the tumor and some based on the protein. These markers are going to help us determine maybe not what they’re going to receive right now in [terms of] treatment, but what options we have to treat them with.

We embed the conversation around using mirvetuximab soravtansine in the light what we have for PARP inhibitors and how far personalized medicine has come in ovarian cancer. If we have patients who never received [testing], I will check and say we have next-generation sequencing, BRCA [testing], FRα [testing],HER2, PD-L1, [and more], just to understand the entire landscape of a patient’s tumor and discuss how to best personalize their treatment.

Why is it important for patients who are receiving mirvetuximab to see an eye specialist?

Lyle: In our experience, eye symptoms related to mirvetuximab soravtansine are extremely common. It’s important for patients to have a baseline eye exam to understand what their status is before they start any treatment. Once they initiate treatment with mirvetuximab soravtansine, patients will still see the ophthalmologist and have eye exams done every other cycle, unless they’re having issues. If I start to see any eye-related symptoms, [such as] blurred vision or dry eyes, I [transition] to them having an eye exam every cycle.

I’m pretty quick to have them see the eye doctor more often than less often. A fair amount [of ocular toxicities] remain at a grade 1 level. Nonetheless, it’s important to see the eye doctor, not only to understand what that baseline exam is, but to help me understand if we need to tweak the dosing schedule of the steroid eye drops. I’ve had eye doctors be instrumental in managing some of these AEs for us.

Arend: Once mirvetuximab soravtansine was FDA approved, we had a multidisciplinary meeting with the ophthalmology department to make sure that we have a go-to physician who understands [these toxicities] so that they can be a part of the conversation with the patient [and explain] that this is likely an AE of the mirvetuximab soravtansine [if it presents]. Sometimes, there will be a lot of patients with glaucoma, cataracts, or other issues that they need to be able to discuss with their ophthalmologist, and the ophthalmologist needs to be able to understand what’s related to the drug and what’s not. Sometimes the steroid eye drops themselves can have effects on other things, such as glaucoma and cataracts. It’s important to make sure that there’s consistency in who the patients are seeing and that the ophthalmology team is familiar with the drug.

What other AEs beyond ocular toxicity associated with mirvetuximab soravtansine require attention?

Lyle: Neuropathy is [also] common with our patients. In some situations, they have been pretreated with chemotherapy agents that have caused some residual peripheral neuropathy. In other cases, neuropathy is an AE they experienced during mirvetuximab soravtansine therapy. We discuss pharmacologic and nonpharmacologic approaches for that. Those symptoms can be managed by us, but if there’s a situation where typical therapies are not effective, we have a cancer neurology clinic. I will utilize their specialist to help me with some of the more significant neuropathy cases. They’re able to do some additional testing and have other kinds of therapies that they can offer patients.

I don’t personally see pneumonitis as often in our patients, although that is certainly an AE that can happen. I make sure to ask my patients about symptoms related to cough, shortness of breath, and any type of respiratory complaints.

Those are kind of the other 2 main AEs that I [consider] with mirvetuximab soravtansine that we’re able to manage to a certain degree, but there are times where we may need to consult someone else to help manage those issues.

How can a multidisciplinary team help manage the AEs of mirvetuximab soravtansine?

Arend: When I was a fellow, it [seemed] like everybody got carboplatin and paclitaxel and we didn’t have any other subspecialties that managed anything. How much this field has become a multidisciplinary field [is notable]. Even [if you’re not using] mirvetuximab soravtansine, having a cardio-oncologist, a psychologist that specializes in oncology, supportive care, [and] an ophthalmology team [is important] in making sure that these patients feel like they have a multidisciplinary team that’s taking care of them. That has changed a lot in the past several years, and it’s important to not be afraid to call in other teams and specialists to ensure that patients get the best care that they can.

How can improper AE management affect the efficacy of mirvetuximab soravtansine?

Lyle: If the AEs are improperly managed that would ultimately lead to some dose interruptions and treatment delays, and that’s where you would run into issues with efficacy.

Arend: As a clinical trialist, when mirvetuximab soravtansine was just in clinical trials there was a lot of inexperience around it. Then there was a phenomenal paper that was published by Kathleen N. Moore, MD, and David M. O’Malley, MD, discussing how to properly manage the AEs of mirvetuximab soravtansine. Initially, there was a lot of fear around the ocular toxicities, and the thought was that this is not a drug that we ever want to bring to market because it’s so toxic.

[We need to] ensure that we understand how to manage the AEs so we don’t unnecessarily stop the drug, dose reduce, or hold the drug, when we can appropriately manage [the AEs]. Even if a patient is going to get treated locally or somewhere that is a far drive [away], we encourage that we see them on a regular basis. We have so much experience [with this agent], and [we] don’t [want the patient] to end up being somewhere where the providers aren’t comfortable with it and have that affect the efficacy of the treatment.

References

1. FDA grants accelerated approval to mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or peritoneal cancer. FDA. November 14, 2022. Accessed January 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant
2. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. March 22, 2024. Accessed January 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian