Nuances in SORAYA Data Highlight Role of Mirvetuximab Soravtansine in FRα-High Platinum-Resistant Ovarian Cancer

Robert L. Coleman, MD, FACOG, FACS

Clinically meaningful responses were demonstrated in subgroup analyses evaluating the sequencing of mirvetuximab soravtansine-gynx (Elahere) in patients with folate receptor alpha–high (FRα-high), platinum-resistant ovarian cancer who received prior bevacizumab (Avastin), according to Robert L. Coleman, MD, FACOG, FACS.¹

Data from the phase 3 SORAYA trial (NCT04296890) showed that patients treated with the antibody-drug conjugate (n = 105) experienced a confirmed objective response rate (ORR) of 32.4% (95% CI, 23.6%-42.2%), including 5 complete responses.2 In a subgroup analysis regarding timing of prior bevacizumab exposure, patients who received the therapy for platinum-sensitive ovarian cancer (n = 94) achieved an ORR of 34.0% (95% CI, 24.6%-44.5%). Those who were given bevacizumab in the platinum-resistant setting (n = 17) experienced an ORR of 17.6% (95% CI, 3.8%-43.4%).¹

Additionally, patients given mirvetuximab soravtansine as a first treatment in the platinum-resistant setting (n = 66) experienced an ORR of 34.8% (95% CI, 23.5%-47.6%) and those who did not (n = 39) experienced an ORR of 28.2% (95% CI, 15.0%-44.9%).¹

Coleman noted that the safety of mirvetuximab soravtansine in SORAYA was consistent with prior data, as there were low-grade reversible ocular and gastrointestinal events that can be managed with supported care. Treatment-related adverse events (AEs) led to discontinuation of the therapy in 9% of patients, 1 being due to an ocular event.

“Currently, mirvetuximab is approved [by the FDA] under an accelerated approval, and many [clinicians] who are treating patients with recurrent ovarian cancer are trying to understand the nuances of the expectations for efficacy in these different settings,” Coleman said. “These data provided more light on the activity when patients received this as a first-line [treatment], the expectation for overall survival [OS] in these settings, [and] the expectation of patients with prior bevacizumab.”

In an interview with OncLive^®, Coleman, chief medical officer of Sarah Cannon Research Institute and an oncologist with Texas Oncology, a practice in The US Oncology Network, discussed the subgroup analysis, which was presented during the2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO), and where the field is headed in attempt to address unmet needs for this patient population.

What were the key topline findings of the SORAYA study?

SORAYA was a single-arm trial [examining] the efficacy of the mirvetuximab soravtansine in patients with platinum-resistant recurrent ovarian cancer who had prior bevacizumab exposure and 1 to 3 lines of prior therapy. We had shown last year that the ORR was over 32% with a duration of response [DOR] of approximately 7 months, and that was quite exciting for us.

This year, we tried to break down the nuances around that activity because patients that have 1 to 3 prior lines of therapy have different expectations for response. We wanted to highlight the differences of the response rates in different lines of therapy as well as the activity in [patients with] prior exposure to bevacizumab and [what was the] OS.

What additional findings were presented at SGO and how does this research further support the use of mirvetuximab soravtansine in this population?

This year we presented analyses on updating the efficacy in those subgroups [of patients] that I mentioned in patients who had received mirvetuximab as their first regimen. [We] also looked at the efficacy with respect to DOR if they had seen this in later lines of their treatment exposure, and in the absence or presence of prior bevacizumab.

What was unique in this analysis was that patients with bevacizumab could have received it in the frontline setting, [the] platinum-sensitive setting, either as initial therapy or in platinum-sensitive recurrent disease, or as platinum-resistant disease. Interestingly, 6 patients in that analysis had received bevacizumab in both settings.

Fortunately, there was consistent activity, even in the highest-risk patients; these are patients who had seen bevacizumab in the platinum-resistance setting and had received it after third- or fourth-line therapy [and] we still saw an ORR of almost 18%. We’re excited about this because it does provide some more clarity on the initial activity that we saw and we’re very hopeful for the [phase 3] MIRASOL trial [NCT04209855], which I hope will confirm this.

What unmet needs remain in this population and how might they be addressed going forward?

Unmet needs in recurrent ovarian cancer are enormous because we have a very hard time curing patients once the disease returns. We keep looking for more efficacious agents that we can hopefully string along to continue to extend that opportunity for prolonged prevention of recurrence, or [that will] at least get patients to delay the progressions that we see that happen frequently.

What is exciting with this particular agent is adding it in combination with other effective agents, such as bevacizumab, or in some of other disease settings combining it with an immune checkpoint inhibitor. Ultimately, we’d like to see this, as we’ve seen with our ongoing trials, added as a maintenance strategy. This is going to open opportunities for patients who are in need of a new drug that has this kind of efficacy.

What is your main message for colleagues regarding this research?

My main message for any colleaguelooking for the analytics on a trial like this is to participate in research. We have so precious few patients that are participating in clinical research, and we have so many questions to answer. Ultimately, that’s how we make forward progress. Research cures cancer [and] this is how we move the needle. Practitioners will get more experience with the drug, it has some unique AEs that we have been able to mitigate, and this then provides more patients with the opportunity to respond to it. It’s important to continue to follow the space.

The research highlights a number of critical points in drug development, and that’s defining a population [for whom] we think a drug like this would work most effectively. In this case it was FRα-high expression. As we learn more about how drugs work in different environments, this information will help to expand where new drugs might fit, including agents that may be potentially responsive at lower levels of FRα and [it will] then broaden the audience that these drugs may be effective for. The future is really bright for development.

What else were you excited to see at SGO?

Much of what we see here are hypothesis-generating exercises. For instance, early on in the sessions, we heard about a novel combination in low-grade serous ovarian cancer. We've seen novel therapy in patients who carry a BRCA mutation. We saw evidence about how we potentially may increase participation in clinical trials and broaden our eligibility criteria. [These are] many factors that are hypothesis generating and that's important.

References

1. Coleman RL. Mirvetuximab soravtansine(MIRV) in patients with platinum-resistant ovarian cancer with high folate receptor alpha (FRα) expression: evaluation of sequence of therapy on anti-tumor activity in the SORAYA study. Presented at: 2023 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 25-28; Tampa, Florida.
2. Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. Published online January 30, 2023. doi:10.1200/JCO.22.01900