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].”

, 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.

 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).

, the FDA granted full approval to mirvetuximab soravtansine in the same patient population as the 2022 indication.

 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; 

 = .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; 

®, 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.

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

: 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, 

 [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?

: 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.

: 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?

: 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?

: 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?

: 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.

: 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.

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

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

Articles

Rebecca Arend, MD, and Kathryn Lyle, CRNP, discuss their approach to managing ocular and other treatment-related toxicities associated with mirvetuximab soravtansine.

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

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, 

 (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.

 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.

“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.”

, 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. 

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

: 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.

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

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

Ritu Salani, MD, discusses the role of mirvetuximab soravtansine in ovarian cancer and the need for specialist involvement in ocular toxicity management.

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

Dr Salani on Managing Mirvetuximab Soravtansine–Associated Ocular Toxicities in Ovarian Cancer

“As we’re using [mirvetuximab soravtansine] more and more, we’re starting to see some newer adverse effects, especially like cataracts. [These] may not be related to the drug, but actually the eye drops, so understanding the nuances of how this drug may affect the eyes and vision is important.”

Ritu Salani, MD, MBA, gynecologic oncologist, director, Gynecologic Oncology, UCLA, UCLA Health, discusses the management of ocular toxicities associated with mirvetuximab soravtansine-gynx (Elahere) in ovarian cancer.

Ocular toxicities are a unique set of adverse effects (AEs) associated with mirvetuximab soravtansine, as well as other antibody-drug conjugates (ADCs), Salani begins. These toxicities can present in various forms, including blurry vision, photophobia (light sensitivity), eye pain, and occasionally, floaters. It is essential to closely monitor these AEs, as they can affect the patient’s visual acuity and overall quality of life, she states.

Given the potential severity of these eye toxicities, collaborating with eye specialists, such as ophthalmologists or optometrists, is crucial, Salani continues. These professionals can help manage these symptoms and ensure that the patient’s eye health is properly addressed. For example, patients may be prescribed eye drops to alleviate symptoms and prevent further complications, Salani details. In clinical practice, it is becoming increasingly important to work with these specialists to assess the role of eye drops in mitigating toxicity, she emphasizes.

Additionally, some newer ocular AEs, such as cataracts, may not necessarily be linked directly to the drug itself but rather to the use of eye drops, Salani notes. This emphasizes the need for a nuanced understanding of how mirvetuximab soravtansine and its associated treatments affect the eyes, she says. Regular eye exams and a tailored approach to eye care are essential components of managing these toxicities effectively. This approach helps to ensure that patients maintain optimal visual function and quality of life while undergoing treatment, Salani concludes.

Videos

Ritu Salani, MD, MBA, discusses the management of ocular toxicities associated with mirvetuximab soravtansine in ovarian cancer.
 

Managing Ocular and Other Adverse Effects Associated With Mirvetuximab Soravtansine in FRα+ Ovarian Cancer | Supplements and Featured Publications

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

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

Dr Salani on Managing Mirvetuximab Soravtansine–Associated Ocular Toxicities in Ovarian Cancer