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Combining Ipilimumab with local treatments improved survival for patients with melanoma

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Bottom Line: Among patients with melanoma, those who received both ipilimumab (Yervoy) and local peripheral treatments such as radiotherapy or electrochemotherapy had significantly prolonged overall survival compared with those who received only ipilimumab, according to a retrospective clinical study.

Journal in Which the Study was Published: Cancer Immunology Research, a journal of the American Association for Cancer Research.

Author: Sebastian Theurich, MD, lecturer and physician-scientist in the Center of Integrated Oncology (CIO) at the University Hospital of Cologne, Germany.

Background: Ipilimumab is an immunotherapy that has revolutionized the treatment of malignant melanoma, a very aggressive type of skin cancer, according to Theurich. About 20 percent 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 try and cure patients with malignant melanoma; rather, they are used to provide relief from symptoms caused by the melanoma tumors, explained Theurich.

How the Study Was Conducted and Results: Theurich 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 ipilimumab only and 45 received ipilimumab and local peripheral treatment to relieve tumor-related symptoms.

Median overall survival for patients receiving ipilimumab and 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, the median overall survival benefit for those receiving ipilimumab and local peripheral treatment remained–117 weeks compared with 46 weeks for those receiving only ipilimumab.

Author Comment: "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," said Theurich. "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," continued Theurich. "Having data from different parts of the world improves the validity of the results, especially if you deal with retrospective analyses. Moreover, all 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," added Theurich. "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."

Limitations: According to Theurich, the main limitations of the study are that the data were not collected prospectively and in a randomized fashion, but the validity of the results is now being tested in prospective clinical trials.

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Funding & Disclosures: The study was in part funded by the University of Cologne (Physician Scientist Program, "Gerok-Rotationsstelle") and the Freie Akademische Gesellschaft Basel, Switzerland. Theurich declares no conflicts of interest.

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Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 36,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 107 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with nearly 19,500 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.AACR.org.

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