K N Moore1, A M Oza2, N Colombo3, A Oaknin4, G Scambia5, D Lorusso6, G E Konecny7, S Banerjee8, C G Murphy9, J L Tanyi10, H Hirte11, J A Konner12, P C Lim13, M Prasad-Hayes14, B J Monk15, P Pautier16, J Wang17, A Berkenblit17, I Vergote18, M J Birrer19. 1. Department of Obstetrics and Gynecology, Stephenson Cancer Center/University of Oklahoma Health Sciences Center, Oklahoma City, USA. Electronic address: kathleen-moore@ouhsc.edu. 2. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada. 3. Department of Gynecologic Oncology, European Institute of Oncology IRCCS; University of Milan-Bicocca, Milan, Italy. 4. Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 5. Gynecology Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS Roma, Rome, Italy. 6. Gynecologic Oncology, Fondazione IRCCS National Cancer Institute, Milan, Italy. 7. Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, USA. 8. Gynaecology, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK. 9. Cancer Trials Ireland and Medical Oncology, Bon Secours Hospital, Cork, Ireland. 10. Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, USA. 11. Oncology, Juravinski Cancer Centre, Hamilton, Canada. 12. Gynecologic Oncology, Memorial Sloan Kettering Cancer Center, New York, USA. 13. Gynecologic Oncology, The Center of Hope Renown Regional Medical Center, Reno, USA. 14. Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, USA. 15. Gynecologic Oncology, Arizona Oncology (US Oncology Network), University of Arizona, Creighton University School of Medicine, Phoenix, USA. 16. Medicine, Gustave Roussy, Villejuif, GINECO, Villejuif, France. 17. Clinical Development, ImmunoGen, Inc., Waltham, USA. 18. Department of Obstetrics and Gynecology and Gynecological Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium. 19. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, USA.
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 receivedchemotherapy. 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.
RCT Entities:
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.
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Authors: Brian C Avanzino; Kirthana Prabhakar; Pranjali Dalvi; Sharon Hartstein; Hannes Kehm; Aarti Balasubramani; Andrew A Boudreau; Ben Buelow; Karen Chang; Laura M Davison; Suhasini Iyer; Vidyut Kalwit; Kristin Lewis Wilson; Harbani K Malik-Chaudhry; Will Pierson; Geovanni Pineda; Udaya S Rangaswamy; Sowmya Saiganesh; Ute Schellenberger; Harshad S Ugamraj; Rodolfovan D Yabut; Roland Buelow; Jocelyn Chapman; Nathan D Trinklein; Katherine E Harris Journal: Oncoimmunology Date: 2022-08-20 Impact factor: 7.723