Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG

Knispel S, Stang A, Zimmer L, Lax H, Gutzmer R, Heinzerling L, Weishaupt C, Pföhler C, Gesierich A, Herbst R, Kaehler KC, Weide B, Loquai C, Utikal J, Terheyden P, Kaatz M, Schlaak M, Kreuter A, Ulrich J, Mohr P, Dippel E, Livingstone E, Becker JC, Weichenthal M, Chorti E, Gronewold J, Schadendorf D, Ugurel S, Berking C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 8

Journal Issue: 1

DOI: 10.1136/jitc-2019-000395

Abstract

BACKGROUND: Immune checkpoint inhibition (ICI) is an essential treatment option in melanoma. Its outcome may be improved by a preceding radiation of metastases. This study aimed to investigate the impact of a preceding radiotherapy on the clinical outcome of ICI treatment. METHODS: This multicenter retrospective cohort study included patients who received anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or anti-programmed cell death protein 1 (PD-1) ICI with or without preceding radiotherapy for unresectable metastatic melanoma. ICI therapy outcome was measured as best overall response (BOR), progression-free (PFS) and overall survival (OS). Response and survival analyses were adjusted for confounders identified by directed acyclic graphs. Adjusted survival curves were calculated using inverse probability treatment weighting. RESULTS: 835 patients who received ICI (anti-CTLA-4, n=596; anti-PD-1, n=239) at 16 centers were analyzed, whereof 235 received a preceding radiotherapy of metastatic lesions in stage IV disease. The most frequent organ sites irradiated prior to ICI therapy were brain (51.1%), lymph nodes (17.9%) and bone (17.9%). After multivariable adjustment for confounders, no relevant differences in ICI therapy outcome were observed between cohorts with and without preceding radiotherapy. BOR was 8.7% vs 13.0% for anti-CTLA-4 (adjusted relative risk (RR)=1.47; 95% CI=0.81 to 2.65; p=0.20), and 16.5% vs 25.3% for anti-PD-1 (RR=0.93; 95% CI=0.49 to 1.77; p=0.82). Survival probabilities were similar for cohorts with and without preceding radiotherapy, for anti-CTLA-4 (PFS, adjusted HR=1.02, 95% CI=0.86 to 1.25, p=0.74; OS, HR=1.08, 95% CI=0.81 to 1.44, p=0.61) and for anti-PD-1 (PFS, HR=0.84, 95% CI=0.57 to 1.26, p=0.41; OS, HR=0.73, 95% CI=0.43 to 1.25, p=0.26). Patients who received radiation last before ICI (n=137) revealed no better survival than those who had one or more treatment lines between radiation and start of ICI (n=86). In 223 patients with brain metastases, we found no relevant survival differences on ICI with and without preceding radiotherapy. CONCLUSIONS: This study detected no evidence for a relevant favorable impact of a preceding radiotherapy on anti-CTLA-4 or anti-PD-1 ICI treatment outcome in metastatic melanoma.

Authors with CRIS profile

Involved external institutions

Universität Duisburg-Essen (UDE) Germany (DE) Universitätsklinikum Mannheim Germany (DE) Universitätsklinikum Essen Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) HELIOS Kliniken Germany (DE) Klinikum der Stadt Ludwigshafen am Rhein gGmbH Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE) SRH Wald-Klinikum Gera Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universitätsklinikum Tübingen Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universität Witten/Herdecke Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Harzklinikum Dorothea Christiane Erxleben Germany (DE) Elbe Kliniken Stade-Buxtehude Germany (DE)

How to cite

APA:

Knispel, S., Stang, A., Zimmer, L., Lax, H., Gutzmer, R., Heinzerling, L.,... Berking, C. (2020). Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG. Journal for ImmunoTherapy of Cancer, 8(1). https://doi.org/10.1136/jitc-2019-000395

MLA:

Knispel, Sarah, et al. "Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG." Journal for ImmunoTherapy of Cancer 8.1 (2020).

BibTeX: Download