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

Abstract

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.

• Authors: Sebastian Theurich, Sacha I Rothschild, Michael Hoffmann, Mario Fabri, Andrea Sommer, Maria Garcia-Marquez, Martin Thelen, Catherine Schill, Ramona Merki, Thomas Schmid, Dieter Koeberle, Alfred Zippelius, Christian Baues, Cornelia Mauch, Christian Tigges, Alexander Kreuter, Jan Borggrefe, Michael von Bergwelt-Baildon, Max Schlaak
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 4 Issue 9 Pg. 744-54 (09 02 2016) ISSN: 2326-6074 [Electronic] United States
• PMID: 27466265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2016 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents, Immunological
• Ipilimumab
• Proto-Oncogene Proteins B-raf

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Immunological (administration & dosage, adverse effects, therapeutic use)
• Combined Modality Therapy
• Female
• Humans
• Ipilimumab (administration & dosage, adverse effects, therapeutic use)
• Kaplan-Meier Estimate
• Male
• Melanoma (drug therapy, immunology, mortality, pathology)
• Middle Aged
• Mutation
• Neoplasm Metastasis
• Neoplasm Staging
• Proto-Oncogene Proteins B-raf (genetics)
• Treatment Outcome
• Young Adult