#VisualAbstract: Mirvetuximab soravtansine-gynx compared to chemotherapy in folate receptor alpha-positive platinum resistant ovarian cancer led to improved survival

1. Mirvetuximab soravtansine-gynx (MIRV) significantly improved progression-free survival, objective response, and overall survival compared to chemotherapy in patients with platinum-resistant, folate receptor alpha (FRα)-positive ovarian cancer

2.  Ocular adverse events were more common with MIRV, which included blurry vision, keratopathy, and dry eyes.

Evidence Rating: Level 1 (Excellent)

Study rundown: Mirvetuximab soravtansine-gynx (MIRV), is an antibody–drug conjugate against folate receptor α (FRα) using the maytansinoid DM4 as a payload. Currently, it is approved for use for treatment of platinum resistant ovarian cancer. The MIRASOL trial was a phase three randomized, open-label controlled trial  to assess the efficacy and safety of MIRV for individuals with folate receptor α (FRα)-positive, platinum-resistant, high-grade serous ovarian cancer in comparison with those receiving chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). Those included had to have undergone one to three prior lines of systemic therapy and experienced disease progression. Inclusion criteria also required high folate receptor α (FRα) expression, and an ECOG performance status score of between 0 and 1. The trial concluded that MIRV showed substantial benefits in progression progression-free survival, objective response, and overall survival when compared to chemotherapy. The trial limits participation to individuals who have undergone one to three lines of systemic therapies, while excluding those with primary refractory disease. This may limit the applicability of the study. While the MIRV treated group had fewer grade 3 adverse events, the trial did report increased ocular adverse events such as blurry vision, keratopathy, and dry eyes. This trial highlights a new standard of care in the platinum refractory space, an area of unmet need.

Click to read the study in NEJM

Relevant reading: Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I

In-Depth [randomized controlled trial]: The MIRASOL trial enrolled 453 individuals with platinum-resistant, FRα-positive ovarian cancer. These individuals were randomized into either the MIRV group or chemotherapy group. Participants received treatment until progression, adverse effects, consent withdrawal, or death. Eligibility criteria included those trialed on one to three prior lines of systemic therapy. Overall, the MIRV group demonstrated significant progression- free survival (PFS) compared to chemotherapy (median PFS 5.62 vs. 3.98 months, p<0.001). Furthermore, overall survival was improved with MIRV (16.46 vs. 12.75 months, p=0.005). Adverse events were fewer in the MIRV group, with less discontinuation (9.2 vs. 15.9%). Ocular adverse events occurred commonly (56%) in the MIRV group which is a specific adverse event to the medication compared to chemotherapy with 1.8% discontinuing the study drug due to ocular adverse events. In platinum-resistant ovarian cancer, MIRV is a promising therapeutic option compared to current cytotoxic options.

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