title: Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma.
abstract: The anti-PD-1 antibodies nivolumab and pembrolizumab are active in metastatic melanoma; however, there is limited data on combining anti-PD-1 antibody and radiotherapy (RT). We sought to review clinical outcomes of patients receiving RT and anti-PD-1 therapy. All patients receiving anti-PD-1 antibody and RT for metastatic melanoma were identified. RT and systemic treatment, clinical outcome, and toxicity data were collected. Fifty-three patients were included; 35 patients received extracranial RT and/or intracranial stereotactic radiosurgery (SRS) and 21 received whole brain radiotherapy (WBRT) (three of whom also received SRS/extracranial RT). Patients treated with extracranial RT or SRS received treatment either sequentially (RT then anti-PD-1,n= 11), concurrently (n= 16), or concurrent "salvage" treatment to lesions progressing on anti-PD-1 therapy (n= 15). There was no excessive anti-PD-1 or RT toxicity observed in patients receiving extracranial RT. Of six patients receiving SRS, one patient developed grade 3 radiation necrosis. In 21 patients receiving WBRT, one patient developed Stevens-Johnson syndrome, one patient developed acute neurocognitive decline, and one patient developed significant cerebral edema in the setting of disease. Response in irradiated extracranial/intracranial SRS lesions was 44% for sequential treatment and 64% for concurrent treatment (p=0.448). Likewise there was no significant difference between sequential or concurrent treatment in lesional response of non-irradiated lesions. For progressing lesions subsequently irradiated, response rate was 45%. RT and anti-PD-1 antibodies can be safely combined, with no detectable excess toxicity in extracranial sites. WBRT and anti-PD-1 therapy is well tolerated, although there are rare toxicities and the role of either anti-PD-1 or WBRT in the etiology of these is uncertain.
authors.affiliation: Melanoma Institute Australia, The University of Sydney , Sydney, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Liniker
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Menzies
authors.affiliation: Crown Princess Mary Cancer Center , Westmead, Sydney, Australia.
authors.forename: B Y
authors.initials: BY
authors.lastname: Kong
authors.affiliation: Crown Princess Mary Cancer Center , Westmead, Sydney, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Cooper
authors.affiliation: Melanoma Institute Australia, The University of Sydney , Sydney, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ramanujam
authors.affiliation: Melanoma Institute Australia, The University of Sydney , Sydney, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Lo
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Crown Princess Mary Cancer Center, Westmead, Sydney, Australia; Macquarie University Health Sciences Centre, Sydney, Australia.
authors.forename: R F
authors.initials: RF
authors.lastname: Kefford
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Mater Hospital, Sydney, Australia.
authors.forename: G B
authors.initials: GB
authors.lastname: Fogarty
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Guminski
authors.affiliation: Crown Princess Mary Cancer Center , Westmead, Sydney, Australia.
authors.forename: T W
authors.initials: TW
authors.lastname: Wang
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Crown Princess Mary Cancer Center, Westmead, Sydney, Australia.
authors.forename: M S
authors.initials: MS
authors.lastname: Carlino
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Mater Hospital, Sydney, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Hong
authors.affiliation: Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.
authors.forename: G V
authors.initials: GV
authors.lastname: Long
keywords: Anti-pd-1 antibody; immunotherapy; melanoma; radiotherapy