Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer
Authors
Kathleen N Moore ; Antoine Angelergues ; Gottfried E Konecny ; Yolanda García ; Susana Banerjee ; Domenica Lorusso ; Jung-Yun Lee ; John W Moroney ; Nicoletta Colombo ; Andrzej Roszak ; Jacqueline Tromp ; Tashanna Myers ; Jeong-Won Lee ; Mario Beiner ; Casey M Cosgrove ; David Cibula ; Lainie P Martin ; Renaud Sabatier ; Joseph Buscema ; Purificación Estévez-García ; Lan Coffman ; Shibani Nicum ; Linda R Duska ; Sandro Pignata ; Fernando Gálvez ; Yuemei Wang ; Michael Method ; Anna Berkenblit ; Diana Bello Roufai ; Toon Van Gorp ; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups
Citation
NEW ENGLAND JOURNAL OF MEDICINE, Vol.389(23) : 2162-2174, 2023-12
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 ; NCT.)
Abstract
BACKGROUND Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor a (FR alpha), is approved for the treatment of platinum-resistant ovarian cancer in the United States. METHODS 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 FRa 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. RESULTS 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%). CONCLUSIONS Among participants with platinum-resistant, FR alpha-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response.