Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I
Mené sur 366 patientes atteintes d'un cancer épithélial de l'ovaire résistant au sels de platine, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité du mirvétuximab soravtansine (un conjugué anticorps-médicament ciblant le récepteur alpha des folates) et d'une chimiothérapie choisie par le médecin (
Background : Mirvetuximab soravtansine is an antibody-drug conjugate comprising a folate receptor-alpha (FR
α)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open label, phase III study FORWARD I compared mirvetuximab soravtansine and investigator’s choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC). Patients and methods
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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 mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival (PFS, RECIST version 1.1, blinded independent central review) in the intention-to-treat (ITT) population and in the prespecified FRα high population. Results
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A total of 366 patients were randomized; 243 received mirvetuximab soravtansine 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 mirvetuximab soravtansine over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% v 10%), CA-125 responses (53% v 25%), and patient reported outcomes (27% v 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% v 44.0%), and fewer events leading to dose reduction (19.8% v 30.3%) and treatment discontinuation (4.5% v 8.3%) were seen with mirvetuximab soravtansine compared to chemotherapy. Conclusions
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In patients with platinum-resistant EOC, mirvetuximab soravtansine did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored mirvetuximab soravtansine, particularly in patients with high FRα expression. Mirvetuximab soravtansine showed a differentiated and more manageable safety profile than chemotherapy.
Annals of Oncology 2021