Recently published in Cancer Research Immunology, a retrospective clinical study from Sebastian Theurich (University Hospital of Cologne, Germany) and colleagues demonstrated that melanoma patients treated with ipilimumab in combination with peripheral therapies, such as radiotherapy or electorchemotherapy, displayed significantly prolonged overall survival compared with patients who were treated with ipilimumab alone.
According to Theurich, approximately 20% of patients who receive this form of immunotherapy achieve resilient responses – a response far greater than historical outcomes of the disease. However, academics and clinicians are aiming to improve this percentage of patients benefiting from ipilimumab.
In order to assess whether current peripheral treatments – most often used to relieve symptoms occurring as a result of the tumor rather than treat the melanoma itself – would improve survival rates, the team analyzed data from 127 malignant melanoma patients who were treated consecutively at cancer centers in Germany and Switzerland.
Of these patients, 82 were treated with ipilimumab alone and 45 were treated with ipilimumab in combination with peripheral therapies for relief of cancer-related symptoms.
Median overall survival for the patients treated with combination therapies was 93 weeks, compared with 42 weeks for those treated with only ipilimumab. Following an exclusion of patients with brain metastasis, due to a skewed distribution between the two groups, the survival benefit for patients receiving combination ipilimumab and peripheral therapy remained evident – 117 weeks compared with 46 weeks for patients receiving the immunotherapy alone.
“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,” commented 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,” 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 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,” concluded 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.”