MIRASOL Trial: Mirvetuximab in Platinum-Resistant Ovarian Cancer

Expert gynecologic oncologists react to data from the MIRASOL trial, which studied mirvetuximab in patients with platinum-resistant ovarian cancer.


Ritu Salani, MD, MBA: We’re going to shift to endometrial cancer, but before we do, there was MIRASOL, [which] was presented today, and I want to highlight some of the new data, because I think they are going to be game-changing or continue to advance the field. I’d love to hear your takes on the MIRASOL presentation from today.

Ursula A. Matulonis, MD: Obviously, it’s really a transformative trial in terms of a practice-changing study. Mirvetuximab was given accelerated approval in November of 2022 FRα-positive recurrent platinum-resistant ovarian cancer. MIRASOL is the confirmatory phase 3 study that’s required by the FDA, showing single-agent mirvetuximab compared with [physicians’] choice of chemotherapy. [There were] improvements in overall response rate, 42% response rate, [which was] really impressive, vs 16% OS benefit for patients receiving mirvetuximab compared with [physicians’] choice of chemotherapy, and then improvements in progression-free survival also benefiting mirvetuximab vs [physicians’] choice of chemotherapy, [which] really exemplified both investigator-assessed end points as well as blinded independent central review.

Ritu Salani, MD, MBA: I think the really nice thing to see was toxicity profile was well characterized and minimal hematologic toxicities, some ocular toxicities. But as we’re getting better at managing these, I think this will be a kind of a learned protocol to manage this.

Matthew A. Powell, MD: I think this also brings up biomarker testing. We talked about HRD [homologous recombination deficiency], BRCA testing. Now, obviously, FRα is important to have in our background on our patients as we plan sequencing down the road, as well as NaPi2b. What else should we be looking for?

Ursula A. Matulonis, MD: Certainly, probably HER2.

Shannon N. Westin, MD, MPH, FACOG: I foresee a panel for ADCs [antibody-drug conjugates], that we could put into our patients with ovarian [cancer], and also kind of swaying into endometrial like that, we’ll be able to get that testing for everybody and say, OK, you get this and you get this, and this is why. It’s an exciting time. I'll just mention adoptive cell therapy as well, which is coming down the pike. They’re typically for solid tumors, once you get through that first HLA hurdle, [and] then we’re looking at tumor testing for those because they often have a very specific target. So, different CAR [chimeric antigen receptor] T-cell therapies that are coming down the pike are going to require testing on the tumor as well.

Bhavana Pothuri, MD: Before we move on, what struck me, of course, [is] I’m so excited about these data. It's a real win for our [patients with] platinum-resistant ovarian cancer, but why do you think the PFS [progression-free survival] benefit was 1.7 months and the OS [overall survival] benefit was 3.7 months? It’s really interesting, right?

Ursula A. Matulonis, MD: Yes, I think Dr Moore was asked that question during the discussion earlier today. I don’t think we totally understand, obviously, and I agree that the hazard ratios for both OS and PFS were the same. And certainly I think the level of responsiveness that you see with a drug like mirvetuximab, and I bet we’ll see that with other ADCs as well; it really improves patients’ quality [of life (QOL)]. They feel better. They don’t have as much symptom burden, [like] we saw that with QOL that was a benefit with mirvetuximab. Even though it was a negative study, patients feel better that they’ll live longer, they’re more symptom free.

Matthew A. Powell, MD: I must speak to the fact that those that are benefiting, benefit for a long duration. So when you start to see that impact on OS being greater, obviously, we’d love to see more patients responding, even at the 40% range is great. But there’s room for improvement, and the new-generation ADCs also looked to be targeting a lower level of FRα. So exciting times, and the list you presented at this meeting of ADCs is staggering. It’s so exciting.

Bhavana Pothuri, MD: We know that ADCs also have an immunogenic effect, and it’s probable that that might be leading to this longer survival that we’re seeing.

Shannon N. Westin, MD, MPH, FACOG: I'll just say the same thing that I say to all my trainees, that it's a point estimate, and you don't know where your patient is on the curve. So yes, there is a median, and that’s our best way of estimating. But the hazard ratio is really what’s important. So if it's a 40% reduction in the risk of death, and you’re where your patient [is] on that curve, [then they] could end up being out 2 years on this, and you never know where that patient fits. So I’m just always very hesitant, and I learned this from my mentor, Rob Coleman, [MD,] to utilize the point estimate rather than the hazard ratio.

Bhavana Pothuri, MD: Yes, and I think that's a good point. As we even continue to do our education, I always use the hazard ratios, and I’m trying to get everyone to think about hazard ratios and not just the PFS differences.

Transcript edited for clarity.

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