As reported in The New England Journal of Medicine by Kathleen N. Moore, MD, and colleagues, the phase III MIRASOL trial has shown improved progression-free and overall survival with mirvetuximab soravtansine-gynx vs chemotherapy in previously treated patients with folate receptor–alpha (FRα)-positive platinum-resistant high-grade serous ovarian cancer.

Kathleen N. Moore, MD

Study Details

In the global open-label trial, 453 patients enrolled from sites in 21 countries beginning in February 2020 were randomly assigned to receive mirvetuximab soravtansine at 6 mg/kg every 3 weeks (n = 227) or investigator’s choice of chemotherapy (n = 226): either paclitaxel (n = 92), pegylated liposomal doxorubicin (n = 81), or topotecan (n = 53). All patients had previously received one to three lines of therapy and had high FRα tumor expression (≥ 75% of cells with ≥ 2+ staining intensity). The primary endpoint was investigator-assessed progression-free survival.

Progression-Free Survival and Other Outcomes

Median progression-free survival was 5.62 months (95% confidence interval [CI] = 4.34–5.95 months) in the mirvetuximab soravtansine group vs 3.98 months (95% CI = 2.86–4.47 months) in the chemotherapy group (P < .001).

Objective response was observed in 42.3% of patients in the mirvetuximab soravtansine group vs 15.9% of those in the chemotherapy group (odds ratio = 3.81, 95% CI = 2.44–5.94), with complete response in 5.3% vs 0%. Median response duration was 6.77 months (95% CI = 5.62–8.31 months) vs 4.47 months (95% CI = 4.17–5.82 months)

Median overall survival was 16.46 months (95% CI = 14.46–24.57 months) in the mirvetuximab soravtansine group vs 12.75 months (95% CI = 10.91–14.36 months) in the chemotherapy group (hazard ratio [HR] = 0.67, 95% CI = 0.50–0.89, P = .005).

Adverse Events

Grade ≥ 3 adverse events occurred in 41.7% of patients in the mirvetuximab soravtansine group vs 54.1% of the chemotherapy group. The most common reported side effects included keratopathy (9.2%), blurred vision (7.8%), and dry eye (3.2%) in the mirvetuximab soravtansine group, and neutropenia (17.4%), anemia (10.1%), and fatigue (5.3%) in the chemotherapy group. Ocular adverse events of any grade occurred in 56.0% of those in the mirvetuximab soravtansine group.

Serious adverse events occurred in 23.9% vs 32.9% of patients. Adverse events led to treatment discontinuation in 9.2% of patients in the mirvetuximab soravtansine group, most commonly blurred vision and pneumonitis (3 patients each), and in 15.9% of the chemotherapy group, most commonly peripheral neuropathy (4 patients), thrombocytopenia (3 patients), and fatigue (3 patients). Fatal adverse events occurred in 2.3% vs 2.4% of patients; treatment-related death occurred in one patient in the mirvetuximab soravtansine group (due to neutropenic sepsis) and in one patient in the chemotherapy group (due to septic shock).

The investigators concluded, “Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with mirvetuximab soravtansine showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response.”

Dr. Moore, of the Stephenson Cancer Center Section of Gynecologic Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by Immuno-Gen. For full disclosures of the study authors, visit nejm.org.