Journal Article

Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer

Lee, Jung-Yun, Buscema, Joseph, Wang, Yuemei, Tromp, Jacqueline, Coffman, Lan, Beiner, Mario, Konecny, Gottfried E., Nicum, Shibani, Angelergues, Antoine, Roszak, Andrzej, Cibula, David, Moroney, John W., Myers, Tashanna, Berkenblit, Anna, Lorusso, Domenica, Estévez-García, Purificación, Banerjee, Susana, Moore, Kathleen N., Colombo, Nicoletta, Martin, Lainie P., Cosgrove, Casey M., Bello Roufai, Diana, Van Gorp, Toon, Method, Michael, Gálvez, Fernando, Lee, Jeong-Won, García, Yolanda, Pignata, Sandro, Duska, Linda R., Sabatier, Renaud

2023

Overview

Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

• Publisher: Massachusetts Medical Society
• Subject: Adverse events / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Biomarkers / Body weight / Cancer therapies / Carcinoma, Ovarian Epithelial - drug therapy / Carcinoma, Ovarian Epithelial - genetics / Chemotherapy / Clinical trials / Design / Doxorubicin / Drug dosages / Drug Resistance, Neoplasm - genetics / FDA approval / Female / Folate Receptor 1 - antagonists & inhibitors / Folate Receptor 1 - genetics / Folic acid / Humans / Immunoconjugates - administration & dosage / Immunoconjugates - adverse effects / Immunoconjugates - therapeutic use / Maytansine - administration & dosage / Maytansine - adverse effects / Maytansine - analogs & derivatives / Maytansine - therapeutic use / Medical prognosis / Monoclonal antibodies / Ovarian cancer / Ovarian Neoplasms - drug therapy / Ovarian Neoplasms - genetics / Paclitaxel / Platinum / Platinum Compounds - pharmacology / Targeted cancer therapy / Topotecan / Tumors