Ocular AEs From Mirvetuximab Soravtansine Do Not Impact HRQOL in FRα+ Platinum-Resistant Ovarian Cancer

No significant association between treatment-emergent ocular adverse effects (AEs) and health-related quality of life (HRQOL) detriments was observed in patients with folate receptor alpha (FRα)–positive platinum-resistant ovarian cancer treated with mirvetuximab soravtansine-gynx (Elahere) during the phase 3 MIRASOL trial (NCT04209855), according to an analysis of patient-reported outcomes (PROs) from the study presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO).

HRQOL outcomes were assessed using the EQ-5D-5L utility score, EORTC QLQ-C30 GHS/QOL score, and EORTC QLQ-C30 PF score. Findings demonstrated that no significant differences in select HRQOL measures were observed between patients with treatment-emergent blurred vision/keratopathy (cohort 1; n = 91) and patients without treatment-emergent ocular AEs (cohort 2; n = 104). Using the EQ-5D-5L scale, data from the primary analysis showed the differences in scores between cohort 1 and cohort 2 were 0.05 (95% CI, –0.02 to 0.13) at week 9 (P = .163), 0.03 (95% CI, –0.05 to 0.13) at week 15 (P = .466), and 0.03 (95% CI, –0.05 to 0.11) at week 21 (P = .481).

Based on EORTC QLQ-C30 GHS/QOL scores, the differences at weeks 9, 15, and 21 were –2.22 (95% CI, –9.04 to 4.60; P = .522), –0.95 (95% CI, –8.56 to 6.65; P = .804), and 0.98 (95% CI, –7.24 to 9.19; P = .814), respectively. Using EORTC QLQ-C30 PF scores, these respective differences were 3.30 (95% CI, –2.46 to 9.07; P = .259), 4.08 (95% CI, –2.71 to 10.87; P = .237), and 1.59 (95% CI, –5.16 to 8.33; P = .641).

“These findings indicate that mirvetuximab soravtansine treatment benefit outweighs the impact of treatment-emergent ocular [AEs] on HRQOL, supporting mirvetuximab soravtansine as the new standard of care for patients with FRα-positive platinum-resistant ovarian cancer,” lead study author Tashanna K. Myers, MD, explained in her presentation.

Myers is a professor of obstetrics and gynecology at UMass Chan Medical School of Baystate Health in Springfield, Massachusetts.

“A sensitivity analysis that broadened the definition of ocular [AEs] from blurred vision/keratopathy to any treatment-emergent ocular [AEs] showed no statistically significant differences in select HRQOL PRO measures across time points,” Myers added.

Cohort 3 (n = 90) comprised patients who experienced any treatment-emergent ocular AEs, and HRQOL outcomes were similar between this group and cohort 2. Using the EQ-5D-5L scores, the difference between cohort 3 and cohort 2 was 0.04 (95% CI, –0.03 to 0.11) at week 9 (P = .216), 0.01 (95% CI, –0.06 to 0.08) at week 15 (P = .703), and –0.01 (95% CI, –0.10 to 0.09) at week 21 (P = .910). Based on EORTC QLQ-C30 GHS/QOL scores, the differences between the 2 cohorts were –1.68 (95% CI, –8.24 to 4.87) at week 9 (P = .613), 0.45 (95% CI, –6.86 to 7.75) at week 15 (P = .903), and –0.25 (95% CI, –8.13 to 7.63) at week 21 (P = .950). Based on the EORTC QLQ-C30 PF scale, these respective differences were 2.64 (95% CI, –2.80 to 8.08; P = .339), 2.39 (95% CI, –4.13 to 8.91; P = .470), and 0.88 (95% CI, –5.46 to 7.21; P = .785).

MIRASOL Background and Trial Design

MIRASOL enrolled patients with histologically confirmed high-grade serous ovarian cancer and platinum-resistant disease, defined as a platinum-free interval of 6 months or less following their last platinum-based chemotherapy regimen. Patients were required to have FRα-positive tumors, characterized by at least 75% of tumor cells with a membrane staining intensity of 2+ or greater by immunohistochemistry.

Prior exposure to bevacizumab (Avastin) and PARP inhibitors was allowed, and patients with BRCA mutations were eligible for enrollment. However, individuals with primary platinum-refractory disease, defined as a platinum-free interval of less than 3 months, were excluded from the study.

Patients were randomly assigned in a 1:1 ratio to receive either mirvetuximab soravtansine at a dose of 6 mg/kg once every 3 weeks or investigator’s choice of chemotherapy, which included paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan. Randomization was stratified based on the choice of chemotherapy regimen (paclitaxel vs PLD vs topotecan) and the number of prior lines of therapy (1 vs 2 vs 3). Treatment was administered until disease progression, unacceptable toxicity, withdrawal of consent, or any other protocol-defined discontinuation criteria were met.

The trial’s primary end point was progression-free survival as assessed by investigators, with a blinded independent central review sensitivity analysis to validate findings. Key secondary end points included overall response rate as determined by investigator assessment, overall survival, and the OV28 abdominal and gastrointestinal subscale score. Additional secondary end points encompassed safety and tolerability, duration of response, CA-125 response, and time to second disease progression.

Exploratory analyses aimed to evaluate HRQOL using patient-reported outcome measures, including the EORTC QLQ-C30, the EQ-5D-5L scale, and additional OV28 subscales, along with the Patient Global Impression of Severity (PGI-S) instrument.

Notably, prior efficacy and safety data from MIRASOL supported the March 2024 full FDA approval of mirvetuximab soravtansine for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have previously received one to three systemic treatment regimens.2

HRQOL Analysis Baseline Patient Characteristics

At the data cutoff of March 6, 2023, 195 patients treated with mirvetuximab soravtansine were included in the primary analysis, including 91 patients in cohort 1 who experienced treatment-emergent blurred vision or keratopathy and 104 patients in cohort 2 who did not develop treatment-emergent ocular effects.1

The median age at baseline was 64 years (range, 37-79) in cohort 1 and 64 years (range, 32-84) in cohort 2. ECOG performance status was 0 in 66% of patients in cohort 1 and 52% of patients in cohort 2; the remainder in both cohorts had an ECOG performance status of 1.

Regarding prior treatment history, 51% of patients in cohort 1 and 40% in cohort 2 had received 3 prior lines of therapy. Prior exposure to PARP inhibitors was documented in 62% and 48% of patients, respectively.

A history of eye disorders was reported in 40% of patients in cohort 1 and 31% in cohort 2; baseline cataracts were present in 36% and 28% of patients, respectively.

The median time on treatment was longer in cohort 1 (26 weeks [range, 3-116]) compared with cohort 2 (12 weeks [range, 0-72]).

Baseline PROs were evaluated using the EQ-5D-5L, EORTC QLQ-C30 GHS/QOL, and EORTC QLQ-C30 PF scales. The mean EQ-5D-5L utility score was 0.74 (SD, 0.21) in cohort 1 and 0.69 (SD, 0.24) in cohort 2. EORTC QLQ-C30 GHS/QOL scores were 67.2 (SD, 21.8) and 61.5(SD, 23.4), respectively; EORTC QLQ-C30 PF scores were 80.1 (SD, 17.5) and 71.4 (SD, 23.8), respectively.

References

1. Myers TK, Moore KN, Gladieff L, et al. Impact of treatment-emergent ocular events on health-related quality of life in patients with FRα-positive platinum-resistant ovarian cancer treated with mirvetuximab soravtansine: results from the MIRASOL study. Presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO); Seattle, WA, March 14-17, 2025.
2. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. Accessed March 22, 2024. Accessed March 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian