PROs Underscore Utility of Mirvetuximab Soravtansine in FRα+ Ovarian Cancer

Gottfried E. Konecny, MD

Patient-reported outcome (PRO) data, complemented by previously reported efficacy findings, for mirvetuximab soravtansine-gynx (Elahere) add to the growing body of evidence supporting the use of the antibody-drug conjugate (ADC) in the treatment of patients with folate receptor-alpha (FRα)–positive, platinum-resistant ovarian cancer, according to Gottfried E. Konecny, MD.

PRO and health-related quality of life (QOL) data from the phase 3 MIRASOL trial (NCT04209855) presented at the 2024 SGO Annual Meeting on Women’s Cancer demonstrated that 21% of evaluable patients treated with mirvetuximab soravtansine (n = 34/162) experienced a 15-point improvement at week 8/9 in abdominal/gastrointestinal (GI) symptom scores per the EORTC QOL Questionnaire OV28 (EORTC QLQ-OV28; P = .2611). Additionally, an 11-point improvement was observed in 29% and 18% of patients, respectively (P = .0318).¹

On March 22, 2024, the FDA granted full approval to mirvetuximab soravtansine for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have previously received 1 to 3 systemic treatment regimens, based on previously reported findings from MIRASOL.²

“[The approval of mirvetuximab soravtansine] represents a new, effective drug that adds value for the care of patients with platinum-resistant ovarian cancer; it does not take away any of the existing options. It is clear progress and opens new avenues for other indications in ovarian cancer,” Konecny explained.

In an interview with OncLive^® during the 2024 SGO Annual Meeting on Women’s Cancer, Konecny discussed the importance of analyzing PROs from MIRASOL and expanded on the QOL data presented at the conference.

Konecny is a medical oncologist in the Department of Gynecologic Medical Oncology and a lead clinician for gynecologic oncology at the University of California, Los Angeles (UCLA), UCLA Health Jonsson Comprehensive Cancer Center.

Editor’s note: This interview was conducted prior to the March 2024 FDA approval of mirvetuximab soravtansine.

OncLive: As background, what was the rationale and design of MIRASOL?

Konecny: The MIRASOL trial aimed to develop a new treatment for [patients with] platinum-resistant, recurrent ovarian cancer, which is an unmet medical need. We have very little to offer patients with platinum-resistant ovarian cancer; standard-of-care [SOC] treatments are associated with short treatment responses and low response rates. It's particularly important [to note] that [these SOC treatments] are often associated with a lot of toxicities that make it very difficult to endure these treatments. There's a clear need for introducing new agents into this space of difficult-to-treat ovarian cancer.

What were the previously reported topline efficacy and safety findings from MIRASOL?

The MIRASOL study met its primary end point, which was progression-free survival [PFS]. When comparing mirvetuximab soravtansine, which is the FRα-targeting ADC with a [maytansinoid] DM4 payload—a potent microtubule inhibitor—improved PFS compared with investigator’s choice of chemotherapy, which was either pegylated liposomal doxorubicin, topotecan, or paclitaxel [HR, 0.65; 95% CI, 0.52-0.81; P <.0001].

[The study] also met a key secondary end point, which was overall survival [OS; HR, 0.67; 95% CI, 0.50-0.88; P = .0046]. Impressively, it meant another key secondary end point, improving overall response rate [ORR] from 16% [95% CI, 12%-22%] to 42% [95% CI, 36%-49%] for [chemotherapy and mirvetuximab soravtansine, respectively]. All 3 end points were met, suggesting that this is a new SOC in platinum-resistant ovarian cancer.

Regarding PROs, how were these measured during this trial?

PROs are a very important aspect, particularly in platinum-resistant ovarian cancer, because these are patients who often have underlying adverse effects [AEs] from prior treatments, and they have reduced general health status. They have treatment-related AEs [TRAEs] from SOC options, and many of these symptoms are often abdominal or gastrointestinal due to the nature of the disease being ovarian cancer and [generally] a history of prior surgeries.

PROs are key because they add value [beyond] assessing ORR, PFS, and OS. How do patients tolerate treatment and what is the QOL while they undergo treatment? In ovarian cancer, [PROs] are particularly important because patients repeatedly receive treatments, and they often have a number of lines of therapy in their treatment history.

Therefore, QOL while undergoing treatments is a key aspect and a tremendous value for these patients. PROs capture that [perspective], and they allow us to compare whether new treatments improve QOL, whether [QOL] remains the same, or [whether] new treatments deteriorate QOL.

In MIRASOL, there were key questionnaires provided to the patients. One, for example, is the EORTC QLQ-C30, which broadly covers global health aspects, such as TRAEs and fatigue. [The study also used] the EORTC QLQ-OV28, which is specific for ovarian cancer.

For example, in the first 6 questions of [EORTC QLQ-OV28], we're focusing on abdominal symptoms and GI symptoms, particularly because patients with ovarian cancer are fraught with abdominal symptoms. [These initial inquiries] pertain to questions such as: Do you have bloating? Do you have abdominal pain? Do you feel early satiety after eating? These are very specific questions regarding abdominal symptoms that allow us to interpret an improvement during treatment and compare [responses] between treatment arms.

What were some of the key findings from the PRO analysis presented at the 2024 SGO Annual Meeting on Women’s Cancer?

You want to understand whether a new treatment leads to an improvement in QOL of life. A key secondary end point of this study was to assess whether patients who received mirvetuximab soravtansine were more likely to have an improvement in abdominal symptoms. You compare the rate of patients who have a meaningful improvement. The big question is: What's meaningful? Experts do not all necessarily agree on what is meaningful.

To analyze [improvement in abdominal symptoms] in this study, patients described their baseline symptoms. These symptoms were depicted on an analog scale from 0 to 100, with 0 meaning no AEs and 100 meaning severe AEs. Patients then rated where their level is during treatment. At weeks 8, 16, and 24, patients were reevaluated, and the change [on the scale] was then compared between treatment arms.

The question then is: Is a 15-point decrease or a 10-point decrease relevant? Most studies look at a 10-point decrease as a significant improvement in GI-reported symptoms in EORTC QLQ-OV28. [MIRASOL used] a very conservative cutoff of 15 points.

When you look at the outcome data, 21% of patients who received mirvetuximab soravtansine in that setting had a significant improvement in abdominal symptoms, as opposed to 15% of patients with SOC. That did not meet statistical significance [P = .2611]; therefore, other end points were examined, including the more traditional use of a 11-point decrease [in abdominal symptoms]. Twenty-nine percent of patients [treated] with mirvetuximab soravtansine who had a [11-point improvement or higher] in abdominal symptoms, as opposed to 18% of patients [treated] investigator’s choice of chemotherapy; this was statistically significant [P = .0318].

Additionally, the assessment of abdominal symptoms over time was compared between treatment arms. At each time point of assessment—week 8, 16, and 24—mirvetuximab soravtansine showed a significant improvement in abdominal symptoms compared with investigator’s choice of therapy. These data are very much in line with the favorable outcomes [for mirvetuximab soravtansine] regarding improvement in PFS, OS, and ORR, and now we have an improvement in a carefully assessed QOL questionnaire.

[These findings] underscore my personal impression that mirvetuximab soravtansine is a well-tolerated treatment, and patients can remain on this drug for an extended time without cumulative toxicity. The data support that. Patients have fewer TRAEs and improvement in their abdominal symptoms when compared with SOC chemotherapy.

How may these findings impact the future use of mirvetuximab soravtansine going forward?

It's important to have a drug that improves PFS and OS, as well as a drug that increases the likelihood of [a patient] responding. However, having data to show that the QOL of the patient will be improved significantly is important and underscores the fact that [mirvetuximab soravtansine] is a valuable addition as a new SOC for the treatment of [patients with FRα-positive], platinum-resistant ovarian cancer.

As the full FDA approval of this drug is pending, where does mirvetuximab soravtansine fit into the ovarian cancer treatment landscape overall?

The drug has proven to be successful in patients with hard-to-treat, platinum-resistant, recurrent ovarian cancer. If [the agent] works well [in that setting], it may have an even greater impact in patients with platinum-sensitive, recurrent disease. Is there value using the drug in combination with other drugs? Could there be value using the drug [as] a maintenance therapy [in patients who have had a good response]?

The fact that [mirvetuximab soravtansine] has high activity, is well tolerated, and has little cumulative toxicity opens a lot of new possibilities to study the drug in settings of patients with ovarian cancer where it may even have a greater impact.

The presented data on PROs support my subjective impression: It is a well-tolerated drug, and patients who receive the treatment have an improvement in their performance and have a reduction in disease-related symptoms, as well as few TRAEs.

References

1. Konecny GE, Moore KN, Lebreton C, et al. Patient-reported outcome results from phase III MIRASOL trial of mirvetuximab soravtansine vs. investigator's choice of chemotherapy in FRα positive platinum-resistant ovarian cancer. Presented at: 2024 SGO Annual Meeting on Women’s Cancer; March 16-18, 2024; San Diego, CA.
2. FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. Accessed March 22, 2024. Accessed March April 24, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian