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Martin LP , Konner JA , Moore KN , Seward SM , Matulonis UA , Perez RP , Su Y , Berkenblit A , Ruiz-Soto R , Birrer MJ
Characterization of folate receptor alpha (FRalpha) expression in archival tumor and biopsy samples from relapsed epithelial ovarian cancer patients: A phase I expansion study of the FRalpha-targeting antibody-drug conjugate mirvetuximab soravtansine
Gynecol Oncol. 2017 Nov;147(2) :402-407
PMID: 28843653 PMCID: PMC6893864 URL: https://www.ncbi.nlm.nih.gov/pubmed/28843653
AbstractPURPOSE: To characterize folate receptor alpha (FRalpha) expression in archival and fresh biopsy tumor samples from relapsed ovarian cancer patients. METHODS: Patients with ovarian tumors amenable to biopsy were eligible to enroll. Eligibility included a minimum requirement of FRalpha positivity in archival tumor samples (>/=25% of cells with >/=2+ staining intensity). Patients received mirvetuximab soravtansine at 6mg/kg once every 3weeks. Core needle biopsies were collected before and after treatment and FRalpha levels assessed by immunohistochemistry. Descriptive statistics were used to summarize the association between receptor expression and response. RESULTS: Twenty-seven heavily pre-treated patients were enrolled. Six individuals (22%) did not have evaluable pre-treatment biopsies due to insufficient tumor cells. The concordance of FRalpha expression in archival and biopsy tissues was 71%, and no major shifts in receptor expression were seen in matched pre- and post-treatment biopsy samples. Adverse events were generally mild (</=grade 2) with keratopathy (48%), fatigue (44%), diarrhea, and blurred vision (each 37%) being the most common treatment-related toxicities. The confirmed objective response rate (ORR) was 22%, including two complete responses and four partial responses. Superior efficacy measures were observed in the subset of patients with the highest FRalpha levels (ORR, 31%; progression-free survival, 5.4months). CONCLUSION: Concordance of FRalpha expression in biopsy versus archival tumor samples suggests that archival tissue can reliably identify patients with receptor-positive tumors and is appropriate for patient selection in mirvetuximab soravtansine clinical trials. Regardless of the tissue source analyzed, higher FRalpha expression was associated with greater antitumor activity.
Notes1095-6859 Martin, Lainie P Konner, Jason A Moore, Kathleen N Seward, Shelly M Matulonis, Ursula A Perez, Raymond P Su, Ying Berkenblit, Anna Ruiz-Soto, Rodrigo Birrer, Michael J Journal Article United States Gynecol Oncol. 2017 Aug 24. pii: S0090-8258(17)31253-2. doi: 10.1016/j.ygyno.2017.08.015.