MIRASOL final analysis: MIRV remains superior to chemo for ovarian cancer

In the final overall survival (OS) analysis of the phase III MIRASOL trial, the survival benefit previously reported with the antibody drug conjugate mirvetuximab soravtansine (MIRV) remains superior to investigator’s choice chemotherapy (ICC) for the treatment of folate receptor alpha-positive, platinum-resistant ovarian cancer (FRα+ PROC).

“MIRV is the first novel treatment to show statistically significant and clinically meaningful OS benefit over ICC in PROC,” said Dr Toon Van Gorp from the University Hospital Leuven Kefir Cancer Institute and BGOG, Leuven, Belgium, during his presentation at SGO 2025.

At 24 months, the estimated OS probability was 34 percent with MIRV and 22 percent with ICC.

After a median follow-up of 30.5 months, the hazard ratio (HR) for OS continued to favour MIRV over ICC, with MIRV recipients having a 32-percent reduction in the risk of death (HR, 0.68, 95 percent confidence interval [CI], 0.54–0.84; p=0.0004). The median OS was 16.85 months for MIRV and 13.34 months for ICC. [SGO 2025, abstract 939696]

These results mirror those observed during the primary analysis after 13.1 months of follow-up (median OS 16.46 vs 12.75 months; HR, 0.67, 95 percent CI, 0.50–0.89; p=0.0046). [N Engl J Med. 2023;389:2162-2174]

The trend for improved OS with MIRV vs ICC was seen across all subgroups, with more profound effects in women with prior exposure to PARPi* maintenance (HR, 0.54, 95 percent CI, 0.40–0.73; p<0.0001) and those on topotecan for ICC (HR, 0.56, 95 percent CI, 0.37–0.86; p=0.0073).

Other outcomes

PFS by investigator was also better with MIRV vs ICC (median 5.59 vs 3.98 months; HR, 0.63, 95 percent CI, 0.51–0.79; p<0.0001), which was sustained beyond the first progression (PFS2; median 11.01 vs 7.59 months; HR, 0.59, 95 percent CI, 0.48–0.73).

Patterns for other efficacy endpoints were also in favour of the experimental agent over ICC, including objective response rate by investigator (41.9 percent vs 15.9 percent; odds ratio, 3.75, 95 percent CI, 2.4–5.85) and duration of response (median 6.93 vs 4.44 months).

Both MIRV and ICC arms had similar proportions of participants with stable disease (38.3 percent vs 40.3 percent), but the former had higher incidences of partial (36.1 percent vs 15.9 percent) and complete (5.7 percent vs 0 percent) responses than the latter.

Compared with the ICC arm, the MIRV arm had lower rates of grade ≥3 treatment-emergent adverse events (TEAEs; 44 percent vs 55 percent), serious TEAEs (22 percent vs 29 percent), and TEAEs leading to discontinuation (6 percent vs 11 percent). There were no treatment-related AEs leading to death or new safety signals.

“Ocular AEs are the typical AEs associated with MIRV use, but there is a mitigation strategy for this and, if necessary, dose modifications [can be done],” said Van Gorp. “[In this analysis,] ocular AEs were mild and reversible in most patients.”

One of the longest follow-ups in PROC

MIRASOL comprised 453 women with ovarian cancer (mean age 62 years) who had platinum-resistant disease and FRα positivity detected by immunohistochemistry. The women were randomized 1:1 to receive either MIRV 6 mg/kg Q3W or ICC (paclitaxel, pegylated liposomal doxorubicin, or topotecan). About two-thirds of the overall cohort had stage III disease, and 85 percent had no/unknown BRCA mutation.

According to Van Gorp, the median follow-up of 30.5 months is one of the longest in any global study in PROC. “MIRV clinical efficacy, along with its well-characterized safety profile, supports MIRV as standard of care for patients with FRα+ PROC.”

Studies of MIRV in earlier lines of therapy and in combination with other treatments are underway.