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

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: Sarah Knispel, Andreas Stang, Lisa Zimmer, Hildegard Lax, Ralf Gutzmer, Lucie Heinzerling, Carsten Weishaupt, Claudia Pföhler, Anja Gesierich, Rudolf Herbst, Katharina C Kaehler, Benjamin Weide, Carola Berking, Carmen Loquai, Jochen Utikal, Patrick Terheyden, Martin Kaatz, Max Schlaak, Alexander Kreuter, Jens Ulrich, Peter Mohr, Edgar Dippel, Elisabeth Livingstone, Jürgen C Becker, Michael Weichenthal, Eleftheria Chorti, Janine Gronewold, Dirk Schadendorf, Selma Ugurel
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 8 Issue 1 (05 2020) ISSN: 2051-1426 [Electronic] England
• PMID: 32371460 (Publication Type: Comparative Study, Journal Article, Multicenter Study)
• Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• CTLA-4 Antigen
• CTLA4 protein, human
• Immune Checkpoint Inhibitors
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Adult
• CTLA-4 Antigen (antagonists & inhibitors)
• Chemoradiotherapy (methods)
• Female
• Humans
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Male
• Melanoma (immunology, mortality, secondary, therapy)
• Middle Aged
• Programmed Cell Death 1 Receptor (antagonists & inhibitors, immunology)
• Progression-Free Survival
• Retrospective Studies
• Skin Neoplasms (immunology, mortality, pathology, therapy)