Реальные результаты лечения от рака яичников в мире после " Мирветуксимаб соравтансин " : результаты работы в университете.

Introduction

After initial treatment with a combination of surgery and systemic chemotherapy, approximately 70–80% of patients with high-grade serous ovarian cancer (HGSOC) experience recurrence within 2–3 years ( Luyckx et al., 2022 ; Wang et al., 2021 ). While most patients with recurrence will die of their disease, advances in treatment options are extending overall survival rates, allowing patients to live longer ( Siegel et al., 2025 ).

Antibody-drug conjugates (ADC) have emerged as promising treatment agents for advanced, recurrent ovarian cancer. These agents work by coupling a cytotoxic chemotherapy “payload” agent to an antibody that binds to a specific receptor. Receptor internalization mobilizes the payload into the cell, where it is decoupled and released, resulting in dose intensification. Folate Receptor Alpha (FRα) is a folate transport protein that is expressed in 90% of patients with ovarian cancer and has limited expression in normal tissue, making it an ideal therapeutic target. Mirvetuximab Soravtansine (MIRV) combines an antibody specific for FRα with DM4, a potent cytotoxic tubulin inhibitor. MIRV is internalized into the cell, where it releases DM4 intracellularly, ultimately leading to cell cycle arrest and apoptosis. DM4 can also diffuse across the cell membrane into neighboring cells and elicit the same result, a phenomenon known as the bystander effect ( Moore et al., 2021 ).

MIRV received accelerated approval in November 2022 for patients with platinum-resistant ovarian cancer patients overexpressing FRα ( Moore et al., 2023 ). In the Mirasol trial, median progression-free survival (PFS) for patients on MIRV was almost 6 months (vs 4 months with chemotherapy, P < 0.001). Overall survival (OS) was significantly longer, and there was less toxicity with MIRV in comparison to conventional chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). Notably, the eligibility criteria restricted enrollment to patients with only 1–3 prior chemotherapy regimens ( Moore et al., 2021 ). In practice, patients with ovarian cancer often receive more than 3 regimens. In addition, high FRα expression was required (immunohistochemistry showing at least 75% of tumor cells with 2+ staining intensity), a criterion that resulted from the FORWARD I trial, which did not meet its primary endpoint of improved PFS when combining medium (50%–74% of cells with 2+ staining intensity) and high (≥75% of cells with 2+ staining intensity) FRα expression ( Moore et al., 2021 ). Additionally, these studies excluded patients who had platinum-refractory disease. Patients with platinum-refractory disease have more limited treatment options with durable responses, yet may still benefit from additional treatment, including ADCs. Finally, eligibility was restricted to patients with high-grade serous cancer, with minimal impairment in Eastern Cooperative Oncology Group Performance Status (ECOG PS 0–1). After multiple lines of treatment, many patients with recurrent HGSOC have impaired ECOG PS; however, many can tolerate and desire further treatment.

Despite these promising results on trial, outcomes in the real-world gynecologic oncology population remain to be fully understood. Our study aims to estimate survival (OS and PFS) for patients with ovarian cancer receiving MIRV and to describe toxicities from MIRV in a general gynecologic oncology population at an academic cancer center and an academic-affiliated private hospital.

Materials and methods

Study design

This retrospective cohort study included patients who received MIRV for recurrent ovarian cancer at a tertiary academic center and NCI-designated cancer center and an academic-affiliated private hospital staffed by the same clinicians. Clinical and demographic data were collected utilizing the electronic health record (EHR). Data were organized by using a defined data collection instrument and stored in RedCap, a secure online database. Institutional review board approval was obtained (IRB ID #: 202504162). Consent requirements were waived due to the retrospective study design. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Eligibility criteria

Eligibility criteria included adult (>18 years of age) patients diagnosed with recurrent ovarian cancer who were treated with MIRV by Washington University School of Medicine Gynecologic Oncology faculty. Identified participants were treated with MIRV between November 2022 and April 2025. November 2022 was selected as the starting date. The index date for entry was the date of initial MIRV treatment. Notably, all expression levels of FRα and ECOG PS were included. Somatic FRα, BRCA, and HRD statuses were evaluated with Caris Life Sciences testing. Germline testing was completed using Myriad MyChoice. Platinum status was recorded from the EHR. Platinum-sensitive status was defined as recurrence six months or longer after the most recent administration of platinum-based chemotherapy, whereas platinum-resistant status was defined as recurrence less than six months after the most recent administration of a platinum-based chemotherapy. Platinum-refractory ovarian cancer was defined as disease progression during or within one month of platinum-based chemotherapy.

Exclusion criteria included patients under the age of 18, no structured activity recorded in the EHR (visits, orders, medication administration), primary malignancy other than ovarian, fallopian tube or primary peritoneal cancer. Eligible patients were followed until the last available follow-up or the date of death during the defined study period.

Clinical outcomes

The primary outcome was PFS, which is defined as the time from the initial dose of MIRV to disease progression or all-cause death, whichever occurred first. If a study patient was still alive at the last follow-up time point, PFS was censored at this time point. Progression dates were gathered from the EHR based on provider documentation that incorporated radiologic findings and physical exam. The secondary outcome was OS, which is defined as the time from the first dose of MIRV to all-cause death. If a study patient was alive at the last follow-up point, OS was censored at that time point.

FRα Caris testing was defined as high (2+ cell staining intensity, ≥ 75% of cells stained), medium (2+ cell staining intensity, 50%–74% of cells stained), low (2+ cell staining intensity, 25%–49% of cells stained), or negative (< 2+ cell staining intensity or < 25% of cells stained). HRD status was recorded from Caris testing. Negative FRα status was retained in the categorization scheme to account for patients whose initial biopsy was negative and who did not receive treatment at that time, but whose subsequent testing demonstrated FRα expression, thus allowing for treatment. HRD status was obtained from Caris testing.

Toxicity grading was determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) classification system. Given the high prevalence of baseline toxicities from prior chemotherapy, only new or worsening toxicities observed during MIRV treatment were recorded from the EMR.

Statistical methods

Primary analysis

The Kaplan-Meier method was utilized to estimate survival distribution functions of PFS and OS. The median PFS and OS were reported for the total study sample. Additionally, the Kaplan Meier method also analyzed PFS and OS based on platinum status and ECOG PS.

Secondary analyses

A multivariable Cox proportional hazard model was applied to assess associations between patient treatment characteristics with PFS and OS after MIRV initiation using the total study sample. Risk factors that were considered included ECOG PS at first MIRV administration, number of prior treatment regimens, platinum status, FRα expression, number of prior treatments, and BMI. Adjusted hazard ratios for the association between the risk factors and death were reported. Additionally, we evaluated whether response to prior taxane therapy was associated with subsequent response to MIRV.

Results

During the defined study period, 66 patients were treated with MIRV. The median age at the first dose of MIRV was 65 years (57.0–74.0 years), 95.5% of patients were white (63/66) and 33.3% were classified as obese based on BMI (22/66). Most (57/66, 86.4%) had an ECOG PS of 0–1. The median number of MIRV cycles received was six (range 3–8). Regarding histology, most patients had high-grade serous disease (93.9%, 62/66). There were two patients with low-grade serous carcinoma (3.0%), one with clear cell carcinoma (1.5%), and one with carcinosarcoma (1.5%). Stage IIIC was the most common stage at initial diagnosis (59.1%, 39/66). Most patients had more than five prior treatment regimens (37.9%, 25/66). With regards to platinum status, 51.5% had platinum-resistant disease (34/66), 25.8% had platinum-sensitive disease (17/66), and 22.7% had platinum-refractory disease (15/66). Most (77.3%, 51/66) patients had high FRα expression on the initial tumor biopsy. Six patients had a change in FRα expression upon the second biopsy. One patient initially had high FRα positivity before MIRV initiation and subsequently had negative FRa status on the second biopsy after exposure to MIRV. The other five patients had an increase in FRα positivity. On MIRV, 69.7% of patients had disease progression (46/66), 9.1% had stable disease (6/66), 14% achieved a partial response (9/66), and 2% achieved a complete response (1/66). At the time of analysis, most patients were alive with disease (59.1%, 39/66), 30.3% were dead of disease (20/66), 7.6% died of intercurrent illness (5/66), and 1.5% had no evidence of disease (1/66) ( Table 1 ).

The median PFS was 5.3 months (95% CI, 4.1–7.1) ( Fig. 1 ) . Patients with ECOG PS >1 had a significantly higher risk of progression or death compared with those with ECOG PS 0–1 (HR 3.21, 95% CI 1.14–8.99; p = 0.027). There was no difference in PFS by BMI (HR 0.65, 95% CI 0.33–1.25; P = 0.19), FRα positivity (HR 1.06, 95% CI 0.46–2.47; P = 0.89), or the number of prior chemotherapy regimens (HR 0.86, 95% CI 0.46–1.61; P = 0.63) ( Table 2 ) . Patients with platinum-refractory cancers had a median PFS of 4.8 months (2.0 to 8.0), those with platinum-sensitive cancers had a median of 6.4 months (3.5 to 16.9), and those with platinum-resistant cancers had a median of 5.2 months (3.1 to 7.1). There was no statistical difference in PFS based on platinum status ( P = 0.68) ( Fig. 3 ) .

As shown in Fig. 1 , the Kaplan-Meier method estimated the median OS for our patient population at 16.4 months (95% CI, 12.4-NE). Patients with ECOG PS >1 had a median overall survival of 6.0 months (0.3-NE) compared to 20.3 months (13.4 to NE) in patients with ECOG PS of 0 or 1 ( P = 0.0006; HR 5.57, 95% CI 1.68–18.54, P = 0.0051) ( Fig. 2 ). There was no statistically significant association between OS and BMI (HR 0.66, 95% CI 0.24–1.82; P = 0.42), FRα positivity (HR 0.55, 95% CI 0.20–1.51; P = 0.24), or the number of prior chemotherapy regimens (HR 1.46, 95% CI 0.60–3.53 ) ( Table 2 ) . Further, the median OS for platinum-refractory tumors was 15.8 (5.9 to NE), platinum-sensitive was 20.3 months (15.4 to NE), and platinum-resistant was 16.4 months (7.0 to NE); there was no statistical difference in median OS based on platinum status ( P = 0.68 ) ( Fig. 3 ) .

MIRV outcomes in relation to prior taxane therapy were evaluated as a secondary analysis. The median number of months between the last taxane therapy and starting MIRV was 15.3 (4.1–39.2). While on taxane therapy, most patients had a complete response (59.1%, 39/66), while about a third (30.3%, 20/66) had progression of disease, and 15.2% stopped due to toxicity (10/66). Other characteristics are presented in Table 1 . Progression on prior taxane therapy was not associated with progression on MIRV ( Table 2 ).

Toxicity was common among the patient sample (90.9%, 60/66). There was a total of 30 reports of grade 3 or higher toxicity. The most common toxicity was ocular toxicity (53.0%, 35/66), with blurred vision as the most common reported side effect (37.9%, 25/66). The second most common toxicity reported was peripheral neuropathy (50%, 33/66), with most patients experiencing grade 1 peripheral neuropathy. Further, 42.4% (28/66) and 33.3% (22/66) of patients experienced hematologic and gastrointestinal toxicity, respectively. Other details regarding toxicity are demonstrated in Table 3 .

Discussion

In this real-world population, treatment with MIRV showed promising results with prolonged survival in most patients. In our study, the median progression-free and overall survivals were similar to those reported in pivotal trials ( Moore et al., 2021 ; Moore et al., 2023 ; Coleman et al., 2024 ). In comparison to these studies, our patient population was not restricted by platinum status, histology, number of prior treatment lines, or ECOG PS. Notably, there was no significant difference in OS or PFS among platinum-refractory, sensitive, or resistant status, although a relatively small retrospective sample means we cannot exclude subtle differences.

Since the FDA approval for MIRV was for recurrent platinum-resistant ovarian cancers, there has been evidence of treatment efficacy in platinum-sensitive cancers ( Alvarez Secord et al., 2025 ). Platinum-refractory ovarian cancer carries a particularly poor prognosis, and effective treatment options remain limited. Most existing studies evaluating OS and PFS with non‑platinum therapies combine patients with platinum-resistant and platinum-refractory disease into one study group. As a result, patients with true platinum-refractory disease are underrepresented, making it difficult to accurately determine treatment-specific OS and PFS in this population ( Pignata et al., 2015 ; Zhou et al., 2024 ; Pujade-Lauraine et al., 2021 ). There are currently no published studies that examine platinum-refractory cancers and long-term clinical outcomes with MIRV treatment, and our study shows that this could be an area for further exploration.

Other studies have restricted patient criteria to patients treated with up to three treatment regimens. Most patients in our cohort had received more than three prior lines of therapy, and this was not associated with worse survival outcomes; importantly, objective responses were still observed among these heavily pretreated patients. Indeed, our results demonstrate that there can be a benefit for MIRV treatment initiation in patients with multiple prior failed treatment regimens. This is consistent with the findings of Johannet et al., who demonstrated that the median PFS was similar in patients who received 1–3 prior lines of therapy versus >3 prior lines of therapy ( Johannet et al., 2025 ). Similarly, most studies have only included patients with high FRα status on somatic testing. For example, FORWARD II trial showed improvement in median PFS to eight months (95% CI 6.8, 10.0) with combination MIRV and bevacizumab regardless of medium or high FRα expression ( Gilbert et al., 2023 ). In our population, FRα status did not show a significant difference in survival; however, we did not stratify by treatment with bevacizumab in addition to MIRV.

Six patients in our population had a change in FRα expression upon the second biopsy: one patient had a decrease in FRα positivity, and five had an increase in FRα positivity. There is no common event or exposure among these patients to understand this change, and these patients were not exposed to MIRV between biopsies. This finding suggests that further future investigations are warranted to study the mechanisms behind the change in FRα positivity and potentially study means to intentionally alter tumors from FRα negative to FRα positive.

Because both taxane chemotherapies and MIRV target microtubule dynamics to induce cell death, response to prior taxane therapy is commonly considered when deciding to initiate MIRV. All patients in our population had a prior exposure to a taxane-containing chemotherapy regimen, and the majority had disease remission after being treated with a taxane regimen. However, there was no association between progression of disease on MIRV and progression of disease on taxane chemotherapy. This differs from the findings presented by Johannet et al., which found that patients whose cancer had previously progressed on a taxane had worse PFS and OS while treated with MIRV ( Johannet et al., 2025 ).

It is unknown whether ECOG PS affects MIRV treatment outcomes, as most pivotal trials excluded patients with PS >1. Most of our patient population (86%) had an ECOG PS that was between 0 and 1, and 14% had a PS >1. Among all the analyzed risk factors, patients with ECOG PS >1 had significantly decreased survival, both PFS and OS. Further, numerous studies have highlighted that patients receiving MIRV are less likely to experience toxicities when compared to patients receiving traditional chemotherapy. Nevertheless, 91% of patients in our population experienced toxicity from MIRV, and there were 30 reports of grade 3 or higher toxicity reported (30/164, 18%). The toxicity profile of MIRV and the patient's ECOG PS should be accounted for when considering the initiation of MIRV.

Our population was unique in that 33% of the total patient population was classified as obese based on BMI. Patients who were classified as obese did not have a significant difference in survival compared to non-obese patients. The published literature is inconsistent regarding the relationship between obesity and survival in patients with ovarian cancer ( Paschou et al., 2025 ; Nagle et al., 2015 ; Bae et al., 2014 ).

Our study had several limitations. This was a retrospective study design, and the sample size was limited. Accurate data collection heavily relied on consistent provider documentation. In addition, concomitant bevacizumab use was not systematically evaluated, limiting our ability to assess added toxicity or disease response in this cohort.

Despite these limitations, our study has numerous important strengths. To our knowledge, this study is one of the few to evaluate survival and toxicity outcomes in a real-world population without strict eligibility criteria seen in pivotal clinical trials. Moreover, our cohort included a meaningful number of patients with platinum-refractory disease, providing clinically relevant information that is scarce in existing literature. Importantly, our findings suggest that an ECOG PS of 0–1 is associated with improved outcomes, underscoring the prognostic importance of functional status in this population. Patients with an ECOG PS greater than one have not been well studied in an exclusively real-world MIRV-treated cohort.

Conclusion

Treatment with MIRV is associated with meaningful gains in progression-free and overall survival among a subset of individuals with recurrent ovarian cancer. ECOG PS should be considered before initiating MIRV, as patients with poorer ECOG PS should be counseled to expect substantially shorter life expectancy than reported in trials. MIRV toxicity is common, and providers should include this in pre-treatment counseling and symptomatic management. Treatment with MIRV may be considered regardless of platinum status, number of treatment lines, and BMI. Further studies evaluating MIRV efficacy in patients with platinum-refractory disease are warranted.

CRediT authorship contribution statement

Anna V. Jones: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Rachel L. Furuya: Writing – review & editing, Data curation, Conceptualization. L. Stewart Massad: Writing – review & editing, Supervision, Project administration. Dong Wang: Visualization, Validation, Software, Methodology, Formal analysis. Mary M. Mullen: Visualization, Validation, Resources, Conceptualization. Brooke E. Sanders: Writing – review & editing, Supervision, Project administration, Methodology, Investigation, Formal analysis, Conceptualization.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mary M. Mullen reports a relationship with Recursion Pharmaceuticals Inc. that includes: employment. Mary M. Mullen reports a relationship with Valinor Discovery that includes: consulting or advisory. Mary M. Mullen reports a relationship with Bioscent Diagnostics that includes: consulting or advisory. Editorial Board for Gyn Onc Reports. Given her role as co-author, she had no involvement in the peer review of this article and had no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to another journal editor. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Anna V. Jones, Rachel Furuya, L. Stewart Massad, Dong Wang, and Brooke Sanders all declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors would like to thank all patients, clinical staff, and research personnel whose participation and support made this study possible. No primary funders or grants were utilized to complete this study.

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