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Efficacy of combined hypo-fractionated radiotherapy and anti-PD-1 monotherapy in
difficult-to-treat advanced melanoma patients
#MMPMID30034949
Roger A
; Finet A
; Boru B
; Beauchet A
; Mazeron JJ
; Otzmeguine Y
; Blom A
; Longvert C
; de Maleissye MF
; Fort M
; Funck-Brentano E
; Saiag P
Oncoimmunology
2018[]; 7
(7
): e1442166
PMID30034949
show ga
Information on the role of radiotherapy in anti-PD-1 monoclonal antibody-treated
melanoma patients is limited. We report on a prospective cohort of advanced
melanoma patients treated simultaneously with radiotherapy and anti-PD-1 therapy
between 01/01/15 and 30/06/16. Tumor evaluations (RECIST 1.1) were performed
every 3 months on radiated and non-radiated lesions. Twenty-five advanced
melanoma patients (64% AJCC stage IV M1c, 64% on second-line treatment or more,
60% with elevated LDH serum levels) were included. Radiotherapy was performed
early (median: 24 days) after the first anti-PD-1 dose in 15 patients with
rapidly progressing symptomatic lesion(s) or later (median: 5.4 months) in 10
patients with progressive disease (PD) despite PD-1 blockade. Radiotherapy was
limited to one organ in 24 patients and consisted mainly of hypo-fractioned
radiotherapy (median dose 26 Gy in 3-5 fractions, 17 patients) or brain
radiosurgery (5 patients). Median follow-up after first anti-PD-1 dose was 16.9 m
(range 2.7-27.4), with 44% of patients alive at last follow-up. For radiated
lesions, rates of complete (CR), partial (PR) responses, stable disease (SD) or
PD were 24%, 12%, 24%, and 32%, respectively. For non-radiated lesions, rates of
CR, PR, SD, and PD were 20%, 19%, 12%, and 40%, respectively. Responses achieved
after radiotherapy for radiated and non-radiated areas were correlated (Pearson
correlation r: 0.89, P<0.0001) suggesting an abscopal effect. Five patients with
CR remained disease-free after discontinuation of anti-PD-1 for a median of
9.5 months. No unusual adverse event was recorded. Hypo-fractionated radiotherapy
may enhance efficacy of anti-PD1 therapy in difficult-to-treat patients.
Controlled studies are needed.
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