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Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

  • Theurich S Department I of Internal Medicine, Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany. Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Germany. Max-Planck-Institute for Metabolism Research, Cologne, Germany. Radio-Immuno-Oncology (RIO) Initiative, University Hospital of Cologne, Cologne, Germany. sebastian.theurich@uk-koeln.de.
  • Rothschild SI Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Germany. University Hospital Basel, Department of Internal Medicine, Medical Oncology, Basel, Switzerland.
  • Hoffmann M Department of Dermatology/Venereology and Skin-Cancer-Center at the CIO, University Hospital of Cologne, Cologne, Germany.
  • Fabri M Department of Dermatology/Venereology and Skin-Cancer-Center at the CIO, University Hospital of Cologne, Cologne, Germany.
  • Sommer A Department of Dermatology/Venereology and Skin-Cancer-Center at the CIO, University Hospital of Cologne, Cologne, Germany.
  • Garcia-Marquez M Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Germany.
  • Thelen M Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Germany.
  • Schill C Division of Hematology/Oncology, Cantonal Hospital of Aarau, Aarau, Switzerland.
  • Merki R Division of Hematology/Oncology, Cantonal Hospital of Aarau, Aarau, Switzerland.
  • Schmid T Medical Oncology, St. Claraspital, Basel, Switzerland.
  • Koeberle D Medical Oncology, St. Claraspital, Basel, Switzerland.
  • Zippelius A University Hospital Basel, Department of Internal Medicine, Medical Oncology, Basel, Switzerland.
  • Baues C Radio-Immuno-Oncology (RIO) Initiative, University Hospital of Cologne, Cologne, Germany. Department of Radiation Therapy, University Hospital of Cologne, Cologne, Germany.
  • Mauch C Department of Dermatology/Venereology and Skin-Cancer-Center at the CIO, University Hospital of Cologne, Cologne, Germany.
  • Tigges C Helios-Klinik St. Elisabeth, Department of Dermatology, Oberhausen, Germany.
  • Kreuter A Helios-Klinik St. Elisabeth, Department of Dermatology, Oberhausen, Germany.
  • Borggrefe J Institute for Diagnostic and Interventional Radiology, University Hospital of Cologne, Cologne, Germany.
  • von Bergwelt-Baildon M Department I of Internal Medicine, Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany. Cologne Interventional Immunology, Department I of Internal Medicine, University Hospital of Cologne, Germany. Radio-Immuno-Oncology (RIO) Initiative, University Hospital of Cologne, Cologne, Germany.
  • Schlaak M Radio-Immuno-Oncology (RIO) Initiative, University Hospital of Cologne, Cologne, Germany. Department of Dermatology/Venereology and Skin-Cancer-Center at the CIO, University Hospital of Cologne, Cologne, Germany.
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  • 2016-07-29
Published in:
  • Cancer immunology research. - 2016
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
Combined Modality Therapy
Female
Humans
Ipilimumab
Kaplan-Meier Estimate
Male
Melanoma
Middle Aged
Mutation
Neoplasm Metastasis
Neoplasm Staging
Proto-Oncogene Proteins B-raf
Treatment Outcome
Young Adult
English Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. Cancer Immunol Res; 4(9); 744-54. ©2016 AACR.
Language
  • English
Open access status
bronze
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Persistent URL
https://folia.unifr.ch/global/documents/17623
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