MIRV treatment effects sustained in PROC despite dose modifications

In a post hoc analysis of the phase III MIRASOL (GOG 3045/ENGOT-ov55) trial, mirvetuximab soravtansine (MIRV) continues to demonstrate clinically meaningful improvements in survival and objective response rate (ORR) in women with platinum-resistant ovarian cancer (PROC) with high folate receptor-alpha (FRα) expression who necessitated dose modifications.

The hazard ratios for progression-free survival (PFS) and overall survival (OS) were 0.58 (95 percent confidence interval [CI], 0.43–0.78; p_nominal=0.0002) and 0.45 (95 percent CI, 0.30–0.68; p_nominal=0.0002), respectively. The median PFS was 7.23 months for MIRV and 5.59 months for investigator’s choice chemotherapy (ICC). As for the median OS, the corresponding numbers were 20.2 and 13.1 months, respectively.

ORR was markedly higher with MIRV than with ICC (60 percent vs 26 percent), yielding an ORR difference of 33.4 percent and an odds ratio of 4.14 (95 percent CI, 2.39–7.18; p_nominal<0.0001). The ORR in the MIRV arm was primarily driven by participants who achieved partial response (51.6 percent), followed by those with stable disease (35.5 percent). Of note, 8.1 percent of MIRV recipients achieved a complete response whereas with ICC, there were none.

Safety-wise, MIRV was tied to lower incidences of grade ≥3 treatment-emergent adverse events (TEAEs; 53 percent vs 72 percent), serious AEs (24 percent vs 39 percent), and discontinuations due to TEAEs (10 percent vs 22 percent). [ESMO Gyn 2024, abstract 44O]

“The [AEs were] predominantly low-grade ocular and gastrointestinal events consistent with that observed in the entire population… MIRV demonstrates a tolerable safety profile compared with ICC,” said Dr Susana Banerjee from The Royal Marsden National Health Services Foundation Trust and Institute of Cancer Research, London, UK, at ESMO Gyn 2024.

The new SoC

An antibody-drug conjugate targeting FRα, MIRV has been shown to improve survival and ORR in patients with high-grade serous PROC compared with ICC. [N Engl J Med 2023;389:2162-2174] The results of this trial have paved the way for MIRV to gain full FDA approval in March 2024 for the treatment of FRα-positive PROC in women who have received one to three prior systemic treatments. “MIRV is the first FDA-approved biomarker-directed therapy for PROC,” Banerjee said.

MIRASOL comprised 453 participants who were randomized 1:1 to receive MIRV 6 mg/kg adjusted to ideal body weight Q3W or ICC (paclitaxel, pegylated liposomal doxorubicin, or topotecan). A little over half of the overall cohort had dose modifications (defined as dose delays, reductions, or interruptions beginning day 1, cycle 1). All patients have been previously exposed to taxanes.

In the MIRV arm (n=124), median age was 63 years. A third had previously received bevacizumab and 55 percent had received poly (ADP-ribose) polymerase (PARP) inhibitors. In the ICC group (n=114), median age was 64 years, and the respective rates of prior exposure to bevacizumab and PARP inhibitors were 45 percent and 59 percent. Almost half of the patients who have had dose modifications had three prior lines of therapy.

“[Our goal was to] understand the impact of dose modifications on the safety and efficacy of MIRV and ICC,” Banerjee explained. “This information is important in clinical practice to help [oncologists] manage patients receiving MIRV.”

“[Our findings suggest that] dose modifications should be considered to maximize the potential of those remaining on [and deriving benefit from MIRV] … MIRV is the new standard of care for patients with FRα-positive PROC,” she concluded.

MIRV is currently under evaluation for the treatment of platinum-sensitive ovarian cancer as monotherapy and in combination with other agents.