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Combining Ipilimumab With Radiotherapy in Advanced Melanoma


The immunotherapy ipilimumab (Yervoy) has revolutionized the treatment of malignant melanoma and resulted in durable responses in 20% to 25% of patients with the cancer. ­Sebastian Theurich, MD, of the Center for Integrated Oncology at the University Hospital of Cologne in Germany, and colleagues investigated the benefits of combining ipilimumab with local peripheral treatments, such as radiotherapy or electrochemotherapy, in patients with advanced melanoma and found the combined therapy significantly prolonged overall survival. Median overall survival for patients receiving the combination therapy was 93 weeks, compared with 42 weeks for those receiving ipilimumab alone. The study was published in Cancer Immunology Research.

The researchers analyzed the clinical data of 127 patients with melanoma consecutively treated with ipilimumab at 4 cancer centers in Germany and Switzerland between 2011 and 2014. The cohort comprised 69 males and 58 females, and the mean age was 61.7 years. Most of the patients had been diagnosed with stage IV disease.

The study patients received ipilimumab (n = 82) or ipilimumab and additional local peripheral treatment, such as radiotherapy, electrochemotherapy, or selective internal radiotherapy (n = 45). Most of the patients received local peripheral treatments during (n = 19; 42.2%) or after (n = 17; 37.8%) ipilimumab therapy, and only 9 patients (20%) had received local peripheral treatment prior to ipilimumab initiation.

Study Findings

The researchers found that the addition of local peripheral treatment to ipilimumab significantly prolonged overall survival (median, 93 vs 42 weeks; unadjusted hazard ratio [HR] = 0.46, P = .0028). Adverse immune-related events were not increased by the combination treatment, and local peripheral treatment–induced local toxicities were in most cases mild.

In a multivariable Cox regression analysis, the researchers demonstrated that the effect of added local peripheral treatment on overall survival remained 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 = .05).

“Our data suggest that the addition of [local peripheral treatment] 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,” concluded the researchers.

Funding for this study was provided by the University of Cologne, Germany.■

Theurich S, et al: Cancer Immunol Res 4:744-754, 2016.



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