Sequencing Advances in High FR-Alpha Ovarian Cancer: MIRASOL Insights

Data from an exploratory analysis of the pivotal phase 3 MIRASOL trial (NCT04209855) were recently unveiled at the European Society for Medical Oncology (ESMO) Congress 2025, opening a broader conversation about optimal treatment sequencing in platinum-resistant ovarian cancer (PROC).¹

The randomized, open-label MIRASOL trial evaluated the efficacy and safety of mirvetuximab soravtansine-gynx (Elahere) vs investigator’s choice of chemotherapy in 453 patients with advanced high-grade PROC whose tumors expressed high levels of folate receptor α (FRα).^2,3 Prior findings demonstrated significant progression-free survival (PFS) and overall survival (OS) improvements when treated with mirvetuximab soravtansine compared with chemotherapy,² positioning the FDA-approved antibody-drug conjugate as a new standard of care for this resistant disease. The present analysis investigated subsequent lines of therapy beyond mirvetuximab soravtansine or chemotherapy received during the trial.

In an interview with Targeted Oncology®, Kathleen N. Moore, MD, MS, professor of gynecologic oncology at the University of Oklahoma College of Medicine and associate director of Clinical Research at Stephenson Cancer Center, reviews the findings from the exploratory analyses and what these new data could mean for optimal treatment sequencing in the platinum-resistant setting.

Targeted Oncology: What were the unmet needs in this patient population that prompted the MIRASOL trial? How did the trial meet these needs?

Kathleen N. Moore, MD, MS: The MIRASOL trial was done in patients with very high-risk ovarian cancer. They had tumors that were designated as platinum-resistant and had the biomarker of being [FRα]-high, a patient population that has had very limited effective therapies until very recently. [This trial], with a demonstrated improvement in [PFS] and [OS] in this population, was the first demonstration that we could improve [OS] with a targeted therapy in the platinum-resistant setting. It was quite an important advance in the beginning for novel therapies for patients with PROC, as [it] led to continued global approval of mirvetuximab soravtansine for this patient population as we speak.

What results were presented at ESMO 2025, and what were some of the most salient or interesting findings?

At ESMO 2025, we presented some exploratory analyses from [MIRASOL], focused on hypothesiz[ing] why we are seeing an [OS] advantage, and what happened after patients discontinued therapy with whichever cohort they were assigned to—either mirvetuximab or standard-of-care chemotherapy—just to see if there were differences in the subsequent therapies received, and whether that could have impacted their [OS].

This was the look at the next systemic anticancer therapy per treatment arm. What we found is that the proportion of patients receiving a next systemic anticancer therapy was very similar for the mirvetuximab arm and the investigator’s chemotherapy arm, which is an important finding. I think many felt that perhaps patients assigned investigator’s choice—which doesn't work very well—were too ill to receive another line of therapy, and those who received mirvetuximab—which had a better efficacy and a differentiated [adverse] effect profile—were maybe healthier and able to receive more systemic therapy, which would, of course, impact [OS]. At least the proportions of patients in each group able to get another line of therapy were exactly the same. And [these results] were pretty similar, even when broke[n] down by the number of prior lines of therapy.

We did also see that taxanes—which, other than mirvetuximab, are our most effective therapy in the platinum-resistant setting—were the most commonly used next systemic anticancer therapy across arms, so it's not surprising and is somewhat of a relief. [Its usage] was higher among patients who were treated with mirvetuximab. Perhaps that contributes to the improved [OS], because they received mirvetuximab, an effective therapy, then went on to receive what is our only other effective therapy, paclitaxel. That's an interesting finding that I think we'll have to follow up on.

We also saw a pretty high rate of platinum-based compounds in this platinum-resistant population, which is interesting and what we see in the real world, where platinums do have a role in platinum-resistant disease and can be quite effective. We saw those in a good proportion of patients, reflecting the real-world nature of this evaluation.

I think that the point here is that there wasn't a big difference in the access to the next line of therapy, which I think is important to say. There wasn't a big drop-off of patients not receiving subsequent lines of therapy, which I think speaks to the improvement in effective agents in the platinum-resistant setting, [as well as] the ability to really talk about sequencing for patients, which we have never been able to do because sequencing assumes that patients are going to be well enough to receive both agents that you're thinking of sequencing. The drop-off was too high in the past to assume you could sequence something, and this really shows us that we are in an era now where sequencing is becoming a very important consideration. As the drop-off between lines of therapy is decreasing, patients are living longer, and so this idea of which medication we use first in what order is becoming more important. I think these sorts of studies speak to that.

What are some next steps or key takeaways that you would like to highlight?

I think the next analysis that we're going to need to do is look at the second or the next [PFS], which will be an extrapolated number because we didn't collect it particularly. But looking at the time to next subsequent therapy minus the time to first subsequent therapy to get a sense of whether patients did as well on their subsequent therapy based on the randomization on MIRASOL would be another interesting look at what happens post mirvetuximab. We'll be working on that for the future.

The MIRASOL study demonstrated definitive improvement in [PFS] and [OS] for patients with FRα-high PROC, and there is some sensitivity to line of therapy as to how effective mirvetuximab is, [thus] reinforc[ing] use of mirvetuximab as the first platinum-resistant option for patients who have FRα-high tumors. As new medications are developed, that statement may need to be changed. But for now, I think that is the take-home from MIRASOL.

I think the second take-home is that patients are healthy enough coming off these therapies to receive subsequent lines of therapy. It brings the importance of starting to think about the sequencing in an evidence-based manner. That's what's going to come next for us, is really some evidence-based sequencing information that will help our patients hopefully live longer and high-quality lives with [PROC]. It's a very different environment for survival and expectations of toxicities in the platinum-resistant space than we've ever had in the past, where it was just such a dismal expectation of efficacy and quality of life. I think we're showing that we can do better by our patients, and this is just some more evidence in that vein.

REFERENCES:

1. Moore, KN. Second progression-free survival and subsequent treatment in patients with folate receptor alpha-positive platinum-resistant ovarian cancer treated with mirvetuximab soravtansine vs. investigator’s choice chemotherapy: Phase 3 MIRASOL trial. Poster presented at: ESMO Congress 2025; October 17-21, 2025; Berlin, Germany.

2. Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;389(23):2162-2174. doi:10.1056/nejmoa2309169

3. A study of mirvetuximab soravtansine vs. investigator's choice (IC) of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha (FRα) expression (MIRASOL). ClinicalTrials.gov. Updated August 27, 2025. Accessed October 27, 2025. https://www.clinicaltrials.gov/study/NCT04209855