Dr Angeles Alvarez Secord on "Exciting" Responses With Mirvetuximab Soravtansine in Platinum-Sensitive Ovarian Cancer

Mirvetuximab soravtansine showed promise for patients with heavily pretreated FRα-positive, platinum-sensitive ovarian cancer—a challenging patient population to treat—in the phase 2 PICCOLO trial. New data from the study presented at the European Society for Medical Oncology (ESMO) Congress 2024 show clinically meaningful antitumor activity and favorable tolerability in patients with FRα-high platinum-sensitive ovarian cancer.

Primary investigator Angeles Alvarez Secord, MD, MHSc, professor of obstetrics and gynecology at Duke Cancer Institute and gynecologic oncologist at Duke Health, discussed the findings presented at ESMO Congress 2024 with The American Journal of Managed Care^® (AJMC^®).

Angeles Alvarez Secord, MD, MHSc

AJMC: What were the main findings of the study, and what are implications of those findings for mirvetuximab soravtansine in FRα-high platinum-sensitive ovarian cancer?

Secord: I'm very excited about the outcome of the study. The main findings are really that this has high evidence of efficacy in individuals who have FRα-positive, platinum-sensitive ovarian cancer, with a response rate in the overall population of 51.9%. And the duration of response was over 8 months, which was very exciting for this group of patients that are really heavily pretreated.

The other aspect here is that there was a subgroup analysis that showed that there was activity across all these various groups—but importantly, activity in patients who have previously been treated with and progressed on a PARP inhibitor. This is a challenging patient population to treat, and the response rate in that group was 45.8%, with a duration of response of over 7 months.

The other aspect was that there were no new concerning safety signals, and it was a very tolerable regimen with overall mild side effects. And the other part of your question was the implications. I'm really hopeful that with these findings, mirvetuximab can be included as one of the tools that we can use for patients with heavily pretreated FRα-expressing platinum-sensitive ovarian cancers.

AJMC: How does the overall response rate seen in this study compare with existing treatments for patients with platinum-sensitive ovarian cancer who have undergone 2 or more prior therapies?

Secord: That is a really challenging question to answer, and we looked at this extensively, trying to find a comparative historical group—and there really isn't one. First, they had to have this significant number of prior lines of therapy. They also, in this current era that we're in, where many individuals receive a PARP inhibitor in the first line, were heavily pretreated, including 81% that had received a PARP inhibitor. So, there is not a historical comparator for this group of patients. In fact, I think that this study will be very helpful to kind of set what is the standard efficacy end point that you like to see for patients who fit this treatment population.

AJMC: What factors contributed to the difference between complete and partial responses, and were there any notable patterns in patient characteristics?

Secord: In terms of complete and partial responses, when you evaluate the waterfall plot, that really clearly shows the depth and breadth of responses. There are many deep and durable responses for patients on this study, and nearly all of the patients derived clinical benefit. Another point I wanted to bring up too, which I think is really interesting point, is the median time to response was actually pretty quick. It was 1.6 months.

In terms of the different subgroup characteristics, we evaluated mirvetuximab across these various different groups based on number of prior lines of therapy, whether or not a BRCA mutation was present, prior PARP exposure, whether or not they progressed on PARP, prior bevacizumab exposure, exposure to both prior PARP inhibitor and bevacizumab, and then their most recent platinum-free interval. And what we found across the board is that mirvetuximab works across all of these groups, and when you talk about different characteristics and response, we found that individuals who had a BRCA mutation and those who were PARP inhibitor naive had response rates of over 70%, so very high response there.

We drilled down further into the subgroup analysis—and one thing I want to be really transparent about is some of these groups had very small numbers, so it limits our interpretation of the data. However, I do think they're promising signals. These groups that are really important are those prior bevacizumab vs no prior bevacizumab. Some patients who were bevacizumab naive, the response was slightly higher, it was 57.1%. If they had received bevacizumab, it was still high, it was 49%. And then in terms of the PARP inhibitor exposure, we discussed the responses there already.

We also have this very unique group—and again, very, very small numbers here—who received prior PARP and bevacizumab, so exposed to both agents, and the response rate in that group is 43.9%. The bar graph illustrates nicely that you have efficacy signals across all of these patient groups, and obviously the magnitude of benefit being higher in some of these groups and others, but certainly appears to be an effective treatment option.

AJMC: How does mirvetuximab soravtansine’s efficacy and safety profile compare with current treatment options for platinum-sensitive ovarian, primary peritoneal, or fallopian tube cancer?

Secord: Well, for the most part, platinum-sensitive ovarian cancers and all of those other cancers are treated with doublet therapy, and often patients receive carboplatin with either a taxane regimen, or liposomal doxorubicin, or gemcitabine. And the addition of bevacizumab can be considered, followed by bevacizumab maintenance. So, we're talking about very different drugs—2 or 3 drugs compared to one drug, and the toxicity profile with mirvetuximab was very favorable.

And this is just anecdotal because this is not a comparative study, but in terms of what we experienced in this heavily pretreated population: one, the risk that I always worry about for patients who are going to do reinduction with carboplatin is their risk of a hypersensitivity reaction, and also the risk of bone marrow suppression when you start to get this many prior regimens. And neurotoxicity can be challenging, too, because of prior taxane and platinum exposure. So, it was really nice to see with this agent that grade 3 and higher side effects were very rare, and most of the side effects were mild and tolerable, which included gastrointestinal, neurosensory, and reversible ocular events. Comparatively to other agents that we use clinically, I felt it was probably a more tolerable regimen.

AJMC: Can you speak to the unmet therapeutic needs that mirvetuximab soravtansine could potentially address?

Secord: Absolutely. I think it's very clear in the platinum-resistant setting, it's been very exciting to have this drug available to us for our patients who have platinum-resistant disease. When I get their FRα and I see that their FRα expression is high and meets that greater than or equal to 75% bar, I'm really thrilled to be able to offer that as an option.

In the platinum-sensitive space, the gap that exists and that this study addressed was heavily pretreated patients who continue to be platinum-sensitive but may not be eligible for repeat therapy with platinum due to hypersensitivity reactions or due to bone marrow suppression. This is a really exciting opportunity to be able to give those patients a drug that has greater efficacy compared with single-agent paclitaxel, liposomal doxorubicin, or gemcitabine, which would be your other options—so a really reasonable, highly effective therapy that is also tolerable.

Overall, there is a strong, urgent, patient-driven need to identify novel therapies that have really favorable side effect profiles for these patients that have received so much prior therapy.

Reference

Secord AA. Mirvetuximab soravtansine (MIRV) in recurrent platinum-sensitive ovarian cancer (PSOC) with high folate receptor-alpha (FRα) expression: Results from the PICCOLO trial. Presented at: European Society of Medical Oncology Congress 2024; September 13-17, 2024; Barcelona, Spain. Abstract 718MO.