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

• DOI: 10.1016/j.annonc.2021.02.017
• Publication Date: 2021-03-02T16:47:07Z
• Authors: K.N. Moore; A.M. Oza; N. Colombo; A. Oaknin; G. Scambia; D. Lorusso; G.E. Konecny; S. Banerjee; C.G. Murphy; J.L. Tanyi; H. Hirte; J.A. Konner; P.C. Lim; M. Prasad-Hayes; B.J. Monk; P. Pautier; J. Wang; A. Berkenblit; I. Vergote; M.J. Birrer
• Keywords: Topotecan; Clinical endpoint; Tolerability; Chemotherapy regimen; Progression-free survival

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).Eligible 1-3 prior lines of therapy whose tumors were positive for FRα expression randomly assigned, 2 : 1 ratio, to receive (6 mg/kg, adjusted ideal body weight) or (paclitaxel, pegylated liposomal doxorubicin, topotecan). primary endpoint was progression-free survival [PFS, Response Evaluation Criteria Solid Tumors (RECIST) version 1.1, blinded independent central review] intention-to-treat (ITT) population prespecified high population.A total 366 randomized; 243 received 109 chemotherapy. endpoint, PFS, did not reach statistical significance either ITT [hazard ratio (HR), 0.98, P = 0.897] (HR, 0.69, 0.049). Superior outcomes over observed all secondary endpoints including improved objective response rate (24% versus 10%), CA-125 responses (53% 25%), patient-reported (27% 13%). Fewer treatment-related grade 3 higher adverse events (25.1% 44.0%), fewer leading dose reduction (19.8% 30.3%) treatment discontinuation (4.5% 8.3%) seen chemotherapy.In EOC, result significant improvement PFS Secondary consistently favored MIRV, particularly expression. showed differentiated more manageable safety profile than