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    CPMCRI scientist co-authors new study of combination immunotherapy for melanoma

    September 21, 2016

    Checkpoint inhibitors are one of the newest classes of drugs to treat melanoma and other types of cancer. When the U.S. Food and Drug Administration (FDA) approved the checkpoint inhibitor nivolumab in 2014 for the treatment of melanoma, the immunotherapy drug brought new hope to the more than 76,000 people in the U.S. diagnosed annually with this deadly form of skin cancer.

    Studies at California Pacific Medical Center (CPMC)’s Center for Melanoma Research and Treatment were key to FDA approval of the drug in melanoma. CPMC entered more patients on the pivotal study than did any other cancer center worldwide.

    Last year, for the first time in any cancer, combination immunotherapies for melanoma were shown to be more effective in shrinking tumors than monotherapy. Adding nivolumab to another commonly used checkpoint inhibitor, ipilimumab, significantly improved objective response rates and progression-free survival in patients with advanced melanoma who had not received previous treatment.

    Preliminary results of a phase 2, multicenter, randomized, double-blind trial were published last year in the New England Journal of Medicine, in a study co-authored by CPMC clinician-scientist David Minor, MD, and led by researchers at Dana-Farber Cancer Institute and Harvard Medical School.

    This week, two-year overall survival outcomes of the phase 2 CheckMate 069 study that Dr. Minor co-authored were reported in Lancet Oncology.
    In the study, 142 patients with advanced melanoma were randomly assigned 2:1 to receive ipilimumab plus nivolumab, followed by nivolumab alone or ipilimumab plus placebo followed by placebo alone. Patients were stratified by BRAF mutation status (about half of all patients with melanoma have mutations in the BRAF gene) and most patients had BRAF wild-type (i.e., mutated) melanoma.

    At a median follow-up of 24.5 months, the two-year survival was 63.8% in patients who received nivolumab plus ipilimumab, and 53.6% in patients receiving ipilimumab alone. The median overall survival has not been reached in either group.

    Treatment-related adverse events (AEs, grades 3-4) were reported in 51 (54%) of 94 patients who received combination therapy, versus nine (20%) of 46 patients who received ipilimumab alone. The most commonly reported AEs were colitis and diarrhea.

    Clinical outcomes were similar for the 33 patients with the BRAF mutant in their melanoma.

    “Combination immunotherapy with nivolumab and ipilimumab might lead to improved outcomes compared with ipilimumab alone in patients with advanced melanoma,” said Dr. Minor. “Dual blockade of key immune checkpoints underlying tumor growth and progression synergistically improves antitumor responses.”

    An editorial accompanying the Lancet Oncology paper noted that “The two-year overall survival data are of much interest… Reliable biomarkers are still needed to enable prediction of response, which might be used to select patients in clinical practice.”

    This same combination of immunotherapy agents is being investigated in phase 2 and 3 clinical trials in cancers of the lung, ovary, and kidney.
    “With these overall survival findings, we have additional support to give new hope to patients with stage IV melanoma, and our knowledge in this area can be applied to other cancers,” said Dr. Minor.

    The study was supported by Bristol-Myers Squibb.