Highlighting Multidisciplinary Ovarian Cancer Care With Oncologists, Ophthalmologists, and Nurses

Oncologists explore the considerations of mirvetuximab soravtansine treatment in platinum-resistant ovarian cancer, highlighting its efficacy and the management of ocular AEs.

Amid the rapidly evolving ecosystem of antibody-drug conjugates (ADCs) in ovarian cancer, a panel of oncologists, an ophthalmologist, and a nurse practitioner discussed their current practices as part of an Around the Practice®program hosted by CancerNetwork. Among the ADCs discussed, mirvetuximab soravtansine-gynx (Elahere), the only one approved by the FDA for ovarian cancer, stood out as the most prominent.1 The management of adverse events (AEs), particularly ocular-related ones, was also heavily discussed.

The panel was led by Leslie Randall, MD, director of Gynecologic Oncology Clinical Research and the Gynecologic Oncology Cancer Service Line at Inova Schar Cancer Institute, Inova Health, in Virginia. She was joined by Marion E. Cole, MD, a medical oncologist at Inova Health System; Asim Farooq, MD, an associate professor of ophthalmology and visual science at the University of Chicago in Illinois; and Mallorie Haba, FNP, a family nurse practitioner at the University of Virginia Health.

Mirvetuximab Soravtansine

Randall / Mirvetuximab soravtansine is the only ADC that’s currently FDA-approved for patients with folate receptor [FR]-α, platinum-resistant ovarian cancer who’ve received 1 to 3 prior lines of systemic treatment. Can you break down the key findings from the pivotal [phase 3 MIRASOL trial (NCT04209855)]?

Cole / The median progression-free survival was 3.6 months with mirvetuximab soravtansine and 3.98 months with standard chemotherapy. An objective response occurred in about 42% of participants on the mirvetuximab arm and 15.9% of patients on the chemotherapy arm. The overall survival was significantly longer with mirvetuximab soravtansine than with chemotherapy: 16.46 months vs 12.75 months.

There was a retrospective, pooled analysis of the [phase 3 SORAYA (NCT04296890)], [phase 3 FORWARD I (NCT02631876)], and MIRASOL studies, and in this pooled analysis, they looked at 682 patients treated with mirvetuximab soravtansine.2 Long-term survival was observed in 34% of patients with a median survival of 28.35 months, and with 66% and 40% alive at 24 and 34 months, respectively. Most of the patients with mirvetuximab soravtansine had 2 to 3 prior lines of therapy, and the most common treatment-related AEs were blurred vision, keratopathy, nausea, dry eye, peripheral neuropathy, fatigue, and diarrhea.

Randall / This is the only phase 3 study in the platinum-resistant space to show an overall survival advantage since the [phase 3 AURELIA trial (NCT00976911)] with the bevacizumab [Avastin] doublets, so the importance of this can’t be underscored.

What is your experience giving this drug to a patient vs giving someone single-agent pegylated liposomal doxorubicin [Doxil]?

Cole / I’ve seen very good responses, and patients do quite well with it. They stay on it for a long time, as long as they’re closely monitored and we watch for AEs…. It’s been a game changer.

Haba / I agree; I’ve seen great benefits from it. I’ve had patients on it for a very long time. It’s great having different AEs than systemic chemotherapy, where a lot of people will feel good on it, too. We have to watch for these new ADC AEs, but as long as we’re educating the patients, and they’re aware to notify us of anything new that they’re concerned about, we’ve seen great outcomes with it.

ADCs in Development

Randall / We’ve got 6 other ADCs that are moving along quickly in development: farletuzumab ecteribulin, rinatabart sesutecan [Rina-S], luveltamab tazevibulin, trastuzumab deruxtecan [Enhertu; T-DXd], datopotamab deruxtecan [Datroway; Dato-DXd], and raludotatug deruxtecan [R-DXd].

It was announced that they were going to stop the development of luveltamab tazevibulin, which is disappointing because it was another FR-targeted ADC that worked in patients who have low-expressing FR-α levels. For mirvetuximab soravtansine, [FR-α expression] has to be 75% to be used as a single agent; luveltamab tazevibulin was working down at 25%; it worked better for a higher level of expression, but there was still activity at the low level. It appeared that this was going to be the mirvetuximab soravtansine for the low expressers; however, the company did announce that they were not moving forward with the development.

Rina-S is also FR-α–targeted with a topoisomerase payload, and this one is hoped to work at the lower levels of FR-α. In its phase 1 data, it showed that it does work at the lower levels, and there’s a phase 3 confirmatory trial that’s currently opening that allows patients with any FR-α expression to enroll.

Then we have the HER2 lines, so we have farletuzumab ecteribulin and T-DXd—anti-HER2. Farletuzumab ecteribulin is less further along in development; it’s still in a phase 1/2 setting. We have T-DXd, and the basket study blew our socks off with very high response rates—around 65% in patients with high- expressing [HER2-negative immunohistochemistry] 2 to 3+.3 This is now [listed by the NCCN] as an option in the recurrent setting. It’s important to test HER2 in our patients, and this is why: because of the availability of T-DXd.

Also, looking at R-DXd, this is a [quadruplet regimen given in 6-week cycles and a topoisomerase] derivative. This showed very high response rates in phase 1, and this is also moving forward in the phase 2 to 3 space. We’re hoping that it will give us [more] diversity of targets.

It is a good thing to have multiple medications in the pipeline, in my opinion. What do you think? Is it too much, just right, or not enough?

Cole / It’s always better to have more options.

Haba / Patients always want more, so [we] need to keep bringing them out.

Randall / Dr Cole, how has that approval of mirvetuximab soravtansine influenced your treatment decisions and sequencing?

Cole / In the platinum-resistance setting, if someone has a high expression of FR-α, it’s usually the first thing I look toward. It’s been a game changer.

Randall / Do you move that before an AURELIA regimen? Technically, the FDA [states]—and even for MIRASOL—[that] patients had to have [a] bevacizumab doublet [in the] first line as platinum resistant. The more people I talk to, we’re saving that for later. We’re using the mirvetuximab soravtansine early.

Cole / Yes, we’ve seen such amazing responses with it. It’s something that needs to be considered.

Randall / Mallorie, what are your biggest concerns when initiating the ADC therapy?

Haba / My biggest thing is to make sure that the patients are aware of what to look for. A lot of these patients have been on systemic chemotherapy, so they’re very comfortable with managing AEs and acknowledging what to look for between either platinum doublets or the maintenance chemotherapy pills. Addressing these other AEs like the ocular toxicities, the pneumonitis, and the [gastrointestinal] differences, as well as making sure that they’re very well educated on those, what to look for, and how to treat them [is important].

Oncology and Eye Care Specialists

Randall / Mallorie, in the academic practice setting, have you established protocols to coordinate care between oncology and eye care specialists? How has that worked for you?

Haba / We do. We’re lucky that we have buy-in with our eye clinic, with our ophthalmologists and optometrists. A lot of times, we’ll try to get patients in the same day, so they have their eye exam in the morning, and then they’ll come and see us, so we’re able to review everything with them and make sure that they’re cleared for treatment.

We have patients [who] travel from far away—2 to 3 hours at a time—so you just have to have buy-in with local optometry and ophthalmology support. If I’m starting with a patient who has a local provider, I make sure I’m printing out the forms they take with them to their appointment. I also print out some information on the drug, and then either I or our pharmacist tries to call a couple of days later. I usually tell them to drop off the paperwork before their eye exam so that the provider can review it, and then if they have any questions about what we’re asking for, we’re able to answer them.

Randall / Dr Farooq, how is your program set up?

Farooq / I’m in an academic practice, and we have a great team of oncologists. We share an electronic medical record, and they know that I’m interested in seeing these patients; a lot of times, they’ll schedule with me, and if my schedule is full, they’ll send me an email, and I’ll facilitate an eye exam promptly. What I’ve learned in talking to community oncologists and ophthalmologists [is that] there are potentially some barriers that need to be addressed in a thoughtful way, especially if a patient does not have an established eye care provider. Starting this drug, one of the things that the manufacturer could help with or that the oncology team could help the patient identify is an eye care provider in their area who’s willing to take this on.

As you indicated in your case, these do require regular eye exams. It’s not just 1 screening exam, and then, “See you in a year” or “See you if you have trouble.” They have to be seen with a regular cadence; at least for many of these drugs, that’s the on-label recommendation. Communication between oncology and ophthalmology or optometry is important in this entire landscape of ADCs.

Randall / Dr Farooq, what are the key elements of monitoring and managing the AEs that are ocular in nature?

Farooq / For many of these ADCs, most of the toxicity that we’re seeing is related to the surface of the eye, and that includes the cornea. The most important elements are symptoms, visual acuity, and slit lamp examination. The exact cadence and dose modification parameters vary depending on the label, and what we’re concerned about based on what was found in the trial. For different agents, there are different intervals for eye examination, but we’re essentially looking for very similar things.

There are some things that are common in ADCs, including what I call pseudo microcysts, these little lesions that we find in the epithelium of the cornea, and with dose holds, for example, they seem to go away. These are reversible, which is a good thing, but the downside is that they can cause shifts in vision. One of the things that I ask patients when they come in is, “Are you having trouble doing your activities of daily living, whether it’s driving, reading, or working on a computer?” It’s important for us to know, it’s important for the patient to know, and it’s important for the oncologist to know because, at the end of the day, these are lifesaving treatments. The patient and the oncologist have to decide whether quality of life is impacted sufficiently to think about holding a dose. One of the things that I often bring up is that, for many drugs, the presence of ocular toxicity can, in some cases, correlate with drug efficacy. In a sense, it’s not a bad thing to see some degree of toxicity because it might correlate with the fact that the drug is working.

References

1. FDA approves mirvetuximab soravtansine-gynx for FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. March 22, 2024. Accessed June 12, 2025. https://tinyurl.com/ynnd6rn7

2. O’Malley DM, Lorusso D, Oaknin A, et al. Characterization of long-term survivors from four clinical trials examining patients with folate receptor alpha–positive recurrent ovarian cancer treated with single-agent mirvetuximab soravtansine. J Clin Oncol. 2024;42(suppl 16):5582. doi:10.1200/JCO.2024.42.16_suppl.5582

3. Andrikopoulou A, Zagouri F, Goula K, et al. Real-world evidence of trastuzumab deruxtecan (T-DXd) efficacy in HER2-expressing gynecological malignancies. BMC Cancer. 2024;24(1):1503. doi:10.1186/s12885-024-13226-1