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

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

Journal: The New England journal of medicine 2023;389(23):2162-2174

PMID: 38055253

Full Text on Atypon View on PubMed

Abstract

BACKGROUND

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.

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 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.

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, 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.).

Address: From the Stephenson Cancer Center Section of Gynecologic Oncology, University of Oklahoma Health Sciences Center, Oklahoma City (K.N.M.); Groupe Hospitalier Diaconesses-Croix Saint Simon, Paris (A.A.), Aix-Marseille Université, INSERM, National Center for Scientific Research, Institut Paoli-Calmettes, Department of Medical Oncology, Marseille (R.S.), and Institut Curie, Saint-Cloud (D.B.R.) - all in France; the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles (G.E.K.); Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí, Universitat Autònoma de Barcelona, Sabadell (Y.G.), Hospital Universitario Virgen del Rocío and Instituto de Biomedicina de Sevilla, Seville (P.E.-G.), and Hospital Universitario de Jaén, Jaen (F.G.) - all in Spain; the Royal Marsden NHS Foundation Trust and Institute of Cancer Research (S.B.) and University College London Cancer Institute (S.N.) - both in London; Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of Sacred Heart, Rome (D.L.), the Gynecologic Oncology Program, European Institute of Oncology IRCCS, and the Department of Medicine and Surgery, University Milan-Bicocca, Milan (N.C.), and Dipartimento Uro-Ginecologico, Istituto Nazionale Tumori di Napoli IRCCS Fondazione G. Pascale, Naples (S.P.) - all in Italy; Yonsei University College of Medicine (J.-Y.L.) and the Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine (J.-W.L.) - both in Seoul, South Korea; the University of Chicago, Chicago (J.W.M.); Wielkopolskie Centrum Onkologii and Poznań University of Medical Sciences, Poznań, Poland (A.R.); Amsterdam University Medical Centers, Amsterdam (J.T.); Baystate Medical Center, Division of Gynecologic Oncology, University of Massachusetts-Chan Baystate, Springfield (T.M.), and ImmunoGen, Waltham (Y.W., M.M., A.B.) - both in Massachusetts; Meir Medical Center, Kfar Saba, Israel (M.B.); Ohio State University, Columbus (C.M.C.); the Department of Gynecology, Obstetrics and Neonatology, First Faculty of Medicine, Charles University, General University Hospital in Prague, Prague, Czech Republic (D.C.); the Division of Hematology-Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (L.P.M.), and Hillman Cancer Center, University of Pittsburgh, Pittsburgh (L.C.) - both in Pennsylvania; Arizona Oncology Associates, PC-HOPE, Tucson (J.B.); the University of Virginia School of Medicine, Charlottesville (L.R.D.); and University Hospital of Leuven, Leuven Cancer Institute, Leuven, Belgium (T.V.G.).

DOI: 10.1056/NEJMoa2309169

Link outs

Free resources

Medical:

Subscription / membership required

Full Text Sources:

MeSH Terms: Female, Humans, Antibodies, Monoclonal, Humanized, Carcinoma, Ovarian Epithelial, Immunoconjugates, Maytansine, Ovarian Neoplasms, Folate Receptor 1, Drug Resistance, Neoplasm, Platinum Compounds