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

H Hirte, M J Birrer, I Vergote, A Berkenblit, J Wang, P Pautier, B J Monk, M Prasad-Hayes, P C Lim, J A Konner, K N Moore, J L Tanyi, C G Murphy, S Banerjee, G E Konecny, D Lorusso, G Scambia, A Oaknin, N Colombo, A M Oza

Journal: Annals of oncology : official journal of the European Society for Medical Oncology 2021;32(6):757-765

PMID: 33667670

Free Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).

PATIENTS AND METHODS

Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population.

RESULTS

A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy.

CONCLUSIONS

In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.

Address: Department of Obstetrics and Gynecology, Stephenson Cancer Center/University of Oklahoma Health Sciences Center, Oklahoma City, USA. Electronic address: [email protected].; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.; Department of Gynecologic Oncology, European Institute of Oncology IRCCS; University of Milan-Bicocca, Milan, Italy.; Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.; Gynecology Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy.; Gynecologic Oncology, Fondazione IRCCS National Cancer Institute, Milan, Italy.; Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, USA.; Gynaecology, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK.; Cancer Trials Ireland and Medical Oncology, Bon Secours Hospital, Cork, Ireland.; Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, USA.; Oncology, Juravinski Cancer Centre, Hamilton, Canada.; Gynecologic Oncology, Memorial Sloan Kettering Cancer Center, New York, USA.; Gynecologic Oncology, The Center of Hope Renown Regional Medical Center, Reno, USA.; Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, USA.; Gynecologic Oncology, Arizona Oncology (US Oncology Network), University of Arizona, Creighton University School of Medicine, Phoenix, USA.; Medicine, Gustave Roussy, Villejuif, GINECO, Villejuif, France.; Clinical Development, ImmunoGen, Inc., Waltham, USA.; Department of Obstetrics and Gynecology and Gynecological Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium.; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, USA.

DOI: 10.1016/j.annonc.2021.02.017