Mirvetuximab Shows Lasting Survival Benefit in Resistant Ovarian Cancer

Toon Van Gorp, MD, PhD

Mirvetuximab soravtansine-gynx (Elahere) continues to demonstrate superior overall survival (OS) and sustained clinical benefits vs investigator’s choice of chemotherapy (ICC) in patients with folate receptor α (FRα)–positive, platinum-resistant ovarian cancer, according to the final analysis of the phase 3 MIRASOL trial (NCT04209855).¹

Presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO), the findings reinforce the role of this antibody-drug conjugate (ADC) as a transformative treatment option for patients with FRα–positive, platinum-resistant ovarian cancer.

The global, randomized, open-label study enrolled 453 patients with FRα-positive, high-grade serous ovarian cancer who had received 1 to 3 prior lines of therapy. At a median follow-up of 30.5 months, mirvetuximab (n = 227) achieved a median OS of 16.85 months (95% CI, 14.36-19.78) compared with 13.34 months (95% CI, 11.37-15.15) with ICC (n = 226), representing a 32% reduction in the risk of death (HR, 0.68; 95% CI, 0.54-0.84; P =.0004). Consistent OS benefits were observed across key subgroups, regardless of prior bevacizumab (Avastin) or PARP inhibitor use, number of prior therapies, or type of chemotherapy.

“Mirvetuximab should be the standard of care in high-grade serous ovarian cancer that expresses folate receptor alpha,” Toon Van Gorp, MD, PhD, told Targeted Oncology^TM, emphasizing the significance of these results.

In the interview, Van Gorp of University Hospital Leuven Kefir Cancer Institute and BGOG, in Leuven, Belgium, discussed these findings and the potential of mirvetuximab to redefine treatment paradigms in ovarian cancer.

Targeted Oncology: Can you discuss the rationale behind the MIRASOL trial and what it sought to investigate?

Van Gorp: The MIRASOL study was a randomized trial, an open-label, phase 3 trial, which randomized patients between mirvetuximab soravtansine and investigator’s choice chemotherapy. In total, we randomized 453 patients, 1:1. The primary end point of the study was progression-free survival by the investigator. This was already published in the New England Journal of Medicine and also presented at ASCO 2023. There were also secondary end points, hierarchical in order: objective response rate, overall survival, and patient-reported outcomes.

Gynecologic cancer illustration: © Crystal Light - stock.adobe.com

What were the key findings from this final analysis, and how do they reinforce the role of mirvetuximab in treating patients with ovarian cancer?

At the primary analysis, we had a follow-up time of 13.1 months. Back then, we had a positive result, of course, in favor of mirvetuximab for progression-free survival, overall survival, and objective response rate. Right now, we have a final analysis after a much longer follow-up, which was 30.5 months—one of the longest follow-up times we have ever seen in this setting, in the platinum-resistant setting, because usually, follow-up times are much shorter.

What we saw was that the results reinforced the protection of mirvetuximab. We had a positive result for overall survival: the median overall survival was 16.9 months for mirvetuximab, and it was 13.3 months for investigator’s choice chemotherapy. This gave a hazard ratio of 0.68, so a reduction of 32% in the risk of death due to the disease. The same was seen with progression-free survival, with a hazard ratio of 0.63—again, a very positive result. When we looked further into the results, including objective response rates, duration of response, and PFS2 (progression after the first recurrence), they were all in line, with positive results for all these end points. So, this is, of course, an excellent result for such a long follow-up in this very difficult-to-treat disease.

It is also very important to look at quality of life and health-related issues. There is another presentation during the SGO meeting about health-related quality of life related to treatment-emergent ocular adverse events. I think this is important because sometimes physicians are a little afraid of the ocular adverse events. I do not think it is necessary to be afraid of this—as long as you know how to handle it and have a good relationship with your ophthalmologist, who can help treat these adverse events. It is important that physicians know this is a well-tolerated drug.

What do these findings mean specifically for patients with platinum-resistant ovarian cancer?

I think this means that we have a better solution than investigator’s choice chemotherapy. I have to mention that this was, of course, a trial for folate receptor alpha–high ovarian cancer, so it’s not for all ovarian cancers—it is specifically for patients who have high folate receptor alpha expression. But for these patients, this definitely means that mirvetuximab is the standard of care because it is much better than standard chemotherapy, and this should be offered to patients as soon as they are confronted with platinum-resistant disease.

What were the long-term safety and tolerability profiles of mirvetuximab, and how does that compare with traditional chemotherapy options?

We had confirmation of the earlier results that we already saw. When we look at grade 3 or higher treatment-emergent adverse events or serious adverse events, we saw that they were less frequent with mirvetuximab. Also, adverse events that resulted in discontinuation of treatment were almost half the number compared with investigator’s choice chemotherapy. This means it is a tolerable treatment.

When we do a deep dive into specific treatment-emergent adverse events, we see less hematological adverse events compared to chemotherapy. There is some neuropathy, but it’s less than with paclitaxel and also less severe—usually grade 1 or 2. We do have some nausea and diarrhea, the same as with chemotherapy. The biggest difference, or something more specific to mirvetuximab, is the ocular toxicity, which is more common with mirvetuximab compared to chemotherapy. But again, this is mainly grade 1 or 2, and we have mitigation strategies with lubricating eye drops and steroid eye drops. If necessary, we do dose modifications when this happens.

What advice do you have for other oncologists who are treating patients using mirvetuximab?

My advice would be that one important aspect is we have to do the folate receptor alpha testing. That is really important. If we do not do it, we will never know whether a patient can receive mirvetuximab or not. Whether you do it at the time of diagnosis or when the patient becomes progressive or platinum-resistant does not matter, as long as we do it. The second thing is, when we have to decide what treatment to give a patient with platinum-resistant disease, I think there should be only one option, and that is mirvetuximab, because it is the best option both for efficacy and safety.

What are the next steps in the research or development of mirvetuximab? Are there plans to explore its use in other settings or combinations?

We know mirvetuximab is better than chemotherapy in platinum-resistant disease, but this is a powerful drug, so I think we should use it in earlier lines. There are ongoing studies in platinum-sensitive disease, looking at combining it with other treatments or giving it as maintenance. I am looking forward to these results because I think this drug should move to earlier lines so more patients can benefit from it.

What unmet needs exist in this space?

Well, it is a difficult-to-treat disease. I think in the future, we’ll have to see what we can do with antibody-drug conjugates and whether we can expand treatments for these patients. I think if we can move our most powerful drugs to earlier lines, maybe we can save more patients. I would love to see this in first line, for example, but I do not know if that will happen. This drug has the potential to replace a drug like paclitaxel, but we don’t have that information yet, so we have to be careful. But I think we should invest more in earlier lines, before the disease becomes platinum-resistant, so we can save more patients.

In a few sentences, what are the key findings from this study?

The key findings are that at the final analysis, there was maintained efficacy for mirvetuximab over investigator’s choice chemotherapy for overall survival, progression-free survival, and objective response rates. Especially the overall survival—prolonging the life of patients with this difficult-to-treat disease is magnificent. There were no new safety signals, so in my opinion, mirvetuximab should be the standard of care in high-grade serous ovarian cancer that expresses folate receptor alpha.

REFERENCE:

1. Van Gorp T, Angelergues A, Konecny G, et al. Final overall survival analysis among patients with FRα-positive, platinum-resistant ovarian cancer (PROC) treated with mirvetuximab soravtansine (MIRV) vs investigator’s choice chemotherapy (ICC) in the phase 3 MIRASOL (GOG 3045/ENGOT-ov55) study. Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 939696.