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Combination therapy of benefit in metastatic melanoma


A new finding suggests that a combination of immunotherapies will help patients with aggressive melanoma resistant to PD-1 inhibitors.


Researchers from the University of California Los Angeles Health Sciences found the combination of ipilimumab and nivolumab provide longer progression-free survival as well as a greater overall response rate to treatment compared to those who received ipilimumab alone. The paper was published in Nature Medicine.


“The results are practice-changing,” said Dr. Antoni Ribas in a press release. “The combination approach should be the preferred drug regimen for people with cancer that has not responded to prior immunotherapy treatment.” He is the study’s senior author, a professor of medicine at the David Geffen School of Medicine at UCLA and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Tumor Immunology Program.


PD-1 inhibitors are a first-line therapy for patients with advanced metastatic melanoma, but more than 50% of melanoma tumours show resistance. When resistance occurs, patients are often switched to CTLA-4 inhibitors.


Prior to this study, it was not clear to clinicians if patients whose cancers are resistant to the PD-1 inhibitors can continue the PD-1 agent in combination with a CTLA-4 inhibitor or if they should be switched to a CTLA-4 inhibitor alone.


“The combination had the potential to better activate the immune system against cancer by simultaneously blocking two main immune checkpoints, increase the immune infiltration in the cancer and thereby overcome resistance to anti-PD-1 alone,” said Dr. Ribas.


In the multicentre study of 91 patients with melanoma who had already received treatment with a PD-1 inhibitor with no response, 68 patients were randomly assigned to receive the combination of ipilimumab and nivolumab and 23 patients received just ipilimumab.


The researchers determined that participants receiving combination therapy had a 37% improvement in progression-free survival compared to participants who received ipilimumab alone. Patients receiving the combination treatment also had higher response rates—28% of patients experienced tumour shrinkage, compared to 9% of those who received ipilimumab alone.


Diarrhea was the most common side effect.


“We found approximately one-third of the patients receiving the immunotherapy combination had improved outcomes,” Dr. Ribas said. “Sequencing immunotherapy treatments as was tested in this study is the next step forward in our efforts to better tailor the treatment options while limiting exposure to side effects. Patients with advanced melanoma can get an anti-PD-1 treatment upfront and only add the anti-CTLA-4 ipilimumab if they do not respond, so only the patients that need the combination are exposed to the increased toxicities.”

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