title: A multireferral centre retrospective cohort analysis on the experience in treatment of metastatic uveal melanoma and utilization of sequential liver-directed treatment and immunotherapy.
abstract: Metastatic uveal melanoma is a rare malignancy with a poor prognosis. To date, systemic therapy has been ineffective; however, there are few data on the benefits of anti-CTLA4 or anti-PD-1 antibodies in sequence with liver-directed therapy. A retrospective cohort analysis was carried out on 37 consecutive patients managed in a tertiary referral centre examining the safety and efficacy of treatment; patterns of care; and impact on survival. The sequential treatment with transarterial chemotherapy (TAC), systemic immunotherapy (IT) and systemic chemotherapy was reviewed. In all, 18 patients in the series received sequential therapy. The median overall survival (OS) was 17 months (n=37), which compared favourably with previously reported series. Patients treated with TAC first or second line had an overall progression-free survival (PFS) of 9 months (n=29) and IT PFS 7 months (n=26). The overall response rate (ORR) for TAC first line was 26% and the disease control rate (DCR) was 65% (n=23). ORR for IT first line was 7%, DCR 77% (n=14). Second-line (cross-over) IT ORR was 16%, DCR 58% (n=12). For second-line (cross-over) TAC, ORR was 50% and DCR was 66% (n=6). Toxicity was manageable. There were no cases of autoimmune hepatitis. In this retrospective small series analysis in uveal melanoma, liver-directed therapy and IT in sequence have shown to be active and reasonably well tolerated. Further prospective clinical trials should clarify the role of these treatments and their potential survival benefit.
authors.affiliation: aDepartment of Medical Oncology, Royal North Shore Hospital bDepartment of Medical Oncology Melanoma Institute Australia cDepartment of Medical Oncology, The University of Sydney, Sydney, New South Wales, Australia dDepartment of Medical Oncology, Istituto Nazionale Tumori 'Fondazione Pascale', Naples, Campania, Italy.
authors.forename: Malinda
authors.initials: M
authors.lastname: Itchins
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Menzies
authors.forename: Meredith
authors.initials: M
authors.lastname: Oatley
authors.forename: Serigne
authors.initials: S
authors.lastname: Lo
authors.forename: Dariush
authors.initials: D
authors.lastname: Douraghi-Zadeh
authors.forename: Timmothy
authors.initials: T
authors.lastname: Harrington
authors.forename: Richard
authors.initials: R
authors.lastname: Maher
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Grimaldi
authors.forename: Alexander
authors.initials: A
authors.lastname: Guminski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016461:Chemoembolization, Therapeutic; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000473:pathology / Q000628:therapy*; D000098943:Uveal Melanoma