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Study: Combining Ipilimumab (Yervoy) With Local Treatments Improves Survival in Melanoma Patients

German study confirms U.S. findings

Melanoma patients who received both ipilimumab (Yervoy, Bristol-Myers Squibb) and local peripheral treatments, such as radiotherapy or electrochemotherapy, had significantly prolonged overall survival compared with those who received only ipilimumab, according to a study published in Cancer Immunology Research. The study was conducted at the University Hospital of Cologne, Germany.

Ipilimumab is an immunotherapy that has revolutionized the treatment of malignant melanoma, according to lead author Sebastian Theurich, MD. Approximately 20% of patients who receive ipilimumab achieve durable responses, which is a major advance compared with historic outcomes, but physician-scientists are looking for ways to increase the percentage of patients who gain long-term benefit from this immunotherapy, he added.

Currently, local peripheral treatments are not used to attempt a cure in patients with malignant melanoma; rather, they are used to provide relief from symptoms caused by the melanoma tumors, Theurich explained.

He and his colleagues analyzed data from 127 patients with malignant melanoma who were treated consecutively at four cancer centers in Germany and Switzerland. Eighty-two patients received only ipilimumab and 45 received ipilimumab plus local peripheral treatments to relieve tumor-related symptoms.

Median overall survival for patients receiving ipilimumab plus local peripheral treatment was 93 weeks compared with 42 weeks for those receiving only ipilimumab. After excluding patients with brain metastases from the analysis (because these patients were not distributed equally among the two treatment groups), patients receiving ipilimumab and local peripheral treatment maintained their median overall survival benefit compared with those receiving only ipilimumab (117 weeks vs. 46 weeks, respectively).

“We found that adding local peripheral treatments, including external radiotherapy, electrochemotherapy, or internal radiotherapy, to systemic ipilimumab treatment doubled survival chances in our patient cohort and did not increase immune-related side effects,” Theurich said. “Importantly, this survival advantage seemed to overcome even traditional risk factors of poor outcomes. This suggests that this combination could be an option for all patients with malignant melanoma, and this is being tested in ongoing prospective clinical trials.

“Our results are concordant with those previously reported for 29 patients treated in the United States with ipilimumab and local radiotherapy,” Theurich continued. "Having data from different parts of the world improves the validity of the results, especially if you deal with retrospective analyses. Moreover, all of our patients were treated with the same dose of ipilimumab, whereas those in the previous study received varying doses because they were being treated in a dose-escalation clinical trial.

“We were also able to begin to investigate the potential immunologic mechanism underlying the benefit of adding local peripheral treatment to ipilimumab,” Theurich added. “It seems that local peripheral treatments activate immune cells, which are then able to attack tumors at sites away from the local treatment site. However, we are investigating this further in prospective studies.”

According to Theurich, the main limitation of the study is that the data were not collected prospectively and in a randomized fashion. The validity of the results, however, is now being tested in prospective clinical trials.

Sources: EurekAlert; July 27, 2016; and Cancer Immunology Research; July 27, 2016.

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