Real-World Data Confirm the Incidence of ADC-Related Ocular Toxicities in Ovarian Cancer

Susan Marie Lang, MD

Although the antibody-drug conjugate (ADC) mirvetuximab soravtansine-gynx (Elahere) is associated with a high rate of ocular toxicity in patients with folate receptor α (FRα)-positive, platinum-resistant ovarian cancer, the real-world incidence of this adverse effect (AE) in this patient population mirrored that observed in the pivotal clinical trial, highlighting the positive impact of close communication between oncologists and ophthalmologists, according to Susan Marie Lang, MD.

In November 2022, the FDA granted accelerated approval to mirvetuximab soravtansine for the treatment of patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 3 prior systemic therapy regimens.¹ The regulatory decision was supported by data from the phase 3 SORAYA trial (NCT04296890), in which treatment with the ADC led to a confirmed, investigator-assessed overall response rate of 31.7% (95% CI, 22.9%-41.6%) in 104 patients. Furthermore, it was noted that in the safety population of the trial (n = 106), the most common any grade eye disorders observed were vision impairment (50%), keratopathy (37%), dry eye (27%), cataract (18%), photophobia (17%), and eye pain (10%).²

Following this FDA approval, Lang and a colleague conducted a study investigating the rate of ocular toxicities observed in a real-world population of patients with platinum resistant high grade serous ovarian cancer (n = 26) treated with mirvetuximab soravtansine.³ The study found that 64% of patients experienced any grade ocular toxicities, with 44%, 24%, 38%, 15%, and 3.8% of patients experiencing keratopathy/corneal disorders, decreased visual acuity, dry eyes, eye pain, and photophobia.

“It’s reassuring that what we found reflects the overall published data we’ve seen so far,” Lang said in an interview with OncLive^® preceding the SGO 2024 Winter Meeting.

In the interview, Lang, a fellow in Medicine in the Division of Gynecologic Oncology at Stanford University in California, discussed research reported from SORAYA that influenced the initiation of this real-world study and key real-world data regarding the incidence of ocular toxicities in patients with ovarian cancer receiving mirvetuximab soravtansine.

OncLive: What served as the rationale for investigating real-world ocular toxicity associated with mirvetuximab soravtansine in patients with ovarian cancer?

Lang: The rationale stems from a couple key points within gynecologic oncology. Platinum-resistant ovarian cancer is a disease process defined by recurrence of ovarian cancer within 6 months from last platinum-based chemotherapy. The reason we care about this is because platinum-resistant recurrent ovarian cancer is challenging to treat. The response rates to subsequent chemotherapy are overall poor and survival times are often short.

Mirvetuximab soravtansine was granted accelerated FDA approval in November 2022. This [regulatory decision] was based on data from the SORAYA trial, and [the agent] was approved for patients with FRα-positive, platinum-resistant recurrent ovarian cancer who had received 1 to 3 prior lines of chemotherapy. [Mirvetuximab soravtansine] represents the first ADC that has been approved for patients with platinum-resistant recurrent ovarian cancer [and this agent] presents an interesting new treatment approach within this disease.

[Importantly, mirvetuximab soravtansine is associated with the AE] of ocular toxicity, and it has a black box warning for this. In light of that, the makers of mirvetuximab soravtansine have published that the overall AE rate for ocular toxicity [with this agent] is 61%, which is high as far as AEs go. Because clinical trials often represent a microcosm of patients, our goal was to assess when you take patients out of the clinical trial setting how different patient factors, which may be less stringent than [the eligibility criteria] of a clinical trial, play into the role of the ocular toxicity we were already seeing with this drug.

What methods were used to conduct this research?

We performed a retrospective study using our single-institution data. [We identified] all patients [who had] conversations about mirvetuximab soravtansine [with their oncologists] and selected patients who had received at least 2 cycles of mirvetuximab soravtansine within our institution following the accelerated FDA approval [of this agent], from approximately November 2022 until the time we collected our data which was September 2023. [We chose 2 as the minimum number of mirvetuximab soravtansine cycles in our study because] within the overall data reported [in SORAYA], the ocular toxicity events occur largely after 1.2 months, which is typically, if you’re giving a medication once every 3 weeks, after the second cycle.

What results from this real-world analysis were presented at the SGO 2024 Winter Meeting?

We identified 26 patients within our institution with varying age ranges, all of whom had high-grade serous ovarian cancers that fit the criteria of platinum-resistant recurrent ovarian cancer. We demonstrated that overall, the [rate of] ocular toxicity [in this real-world population] seemed to be similar [to that observed in the population of patients who received mirvetuximab soravtansine in SORAYA, which was 61%]. Among our patients, 64% had ocular toxicity. The most common AE we saw was keratopathy which is a common finding [among] the ocular toxicities [associated with] this medication.

One area we found most interesting was the rate of decreased visual acuity in our patients. Interestingly, we know from published data that a fair number of patients [who receive mirvetuximab soravtansine] report visual changes. [These changes are not] broken down into any specifics and include a lot of varying categories such as decreased acuity, visual blurriness, and other changes. We evaluated the rate of decreased acuity in our patients and found that 24% experienced decreased visual acuity during treatment.

[We also investigated] the number of patients who required escalation of care due to ocular AEs and whether this [care was delivered in the form of] an emergency department visit for visual changes or increased visits with ophthalmologists within our system or outside our system. We found that approximately 15% of our patients had escalation of care due to ophthalmologic-related AEs.

What is your main message for colleagues regarding this research?

[All practitioners have concerns] when trying to apply [data derived from] strictly selected patient populations to our own patient populations. To see that overall [in our study] there weren’t major differences so far [between the SORAYA and real-world populations] represents the importance of the ongoing relationship we have with our ophthalmology colleagues when it comes to the care of our patients receiving mirvetuximab soravtansine.

What are the next steps for this research?

Although we see a high rate of ocular toxicity [with mirvetuximab soravtansine], which is reproducible in our patient population, we can mitigate this AE with the use of steroids and lubricating eye drops, as well as with the assistance of our ophthalmology colleagues. In the future, we aim to identify patients [receiving mirvetuximab soravtansine] who are at the highest risk of [developing] ocular toxicities and [determine] an underlying mechanism for that. We don’t have [those data] thus far. However, aiming to identify and address risk factors for this AE could add to our ability to further care for our patients and hopefully [contribute to] continued success with this medication.

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 January 25, 2024. https://www.businesswire.com/news/home/20221104005657/en/ImmunoGen-Announces-FDA-Accelerated-Approval-of-ELAHERE%E2%84%A2-mirvetuximab-soravtansine-gynx-for-the-Treatment-of-Platinum-Resistant-Ovarian-Cancer
2. Elahere. Prescribing information. ImmunoGen Inc; 2022. Accessed January 25, 2024. https://www.elahere.com/pdf/prescribing-information.pdf
3. Lang SM, Litkouhi B. Evaluation of real-world ocular toxicity during treatment with mirvetuximab soravtansine. Presented at: SGO 2024 Winter Meeting. January 25-27, 2024; Olympic Valley, California. Poster 530232.