Universität zu Köln

Knispel, Sarah, Stang, Andreas, Zimmer, Lisa, Lax, Hildegard, Gutzmer, Ralf, Heinzerling, Lucie, Weishaupt, Carsten, Pfoehler, Claudia, Gesierich, Anja, Herbst, Rudolf, Kaehler, Katharina C., Weide, Benjamin, Berking, Carola, Loquai, Carmen, Utikal, Jochen, Terheyden, Patrick, Kaatz, Martin, Schlaak, Max, Kreuter, Alexander, Ulrich, Jens, Mohr, Peter, Dippel, Edgar, Livingstone, Elisabeth, Becker, Juergen C., Weichenthal, Michael, Chorti, Eleftheria, Gronewold, Janine, Schadendorf, Dirk and Ugurel, Selma (2020). Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG. J. Immunother. Cancer, 8 (1). LONDON: BMJ PUBLISHING GROUP. ISSN 2051-1426

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knispel, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Stang, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Lax, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutzmer, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinzerling, Lucie UNSPECIFIED UNSPECIFIED UNSPECIFIED Weishaupt, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfoehler, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Gesierich, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Herbst, Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaehler, Katharina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weide, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Berking, Carola UNSPECIFIED UNSPECIFIED UNSPECIFIED Loquai, Carmen UNSPECIFIED UNSPECIFIED UNSPECIFIED Utikal, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Terheyden, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaatz, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlaak, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreuter, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Ulrich, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohr, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Dippel, Edgar UNSPECIFIED UNSPECIFIED UNSPECIFIED Livingstone, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Juergen C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weichenthal, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Chorti, Eleftheria UNSPECIFIED UNSPECIFIED UNSPECIFIED Gronewold, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schadendorf, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Ugurel, Selma UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-349491
DOI:	10.1136/jitc-2019-000395
Journal or Publication Title:	J. Immunother. Cancer
Volume:	8
Number:	1
Date:	2020
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2051-1426
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BRAIN METASTASES; STEREOTACTIC RADIOSURGERY; RADIATION-THERAPY; IPILIMUMAB IMMUNOTHERAPY; CONCURRENT RADIOTHERAPY; SURVIVAL; PEMBROLIZUMAB; EFFICACY; CANCER; SAFETY Multiple languages Oncology; Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34949