What you need to know
John Theurer Cancer Center (JTCC) was a leading center in the DREAMseq trial, a large phase III randomized study that compared immunotherapy 1st (Ipi + Nivo) versus targeted therapies 1st (dabrafenib (and trametinib) in patients with advanced melanoma.
This trial was stopped early due due to definitive results showing that the immunotherapy combination given 1st reduced progression by 20% and improved the 2 year overall survival by 38%.
The findings were presented November 16, 2021, at the inaugural American Society of Clinical Oncology (ASCO) Virtual Plenary Series.
The treatment of melanoma was changed by immunotherapy, particularly checkpoint inhibitor combinations Ipilimumab and Nivolumab. About half melanoma cases carry mutations in key proteins that control cell growth such as BRAF, and which can be targeted with a combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). DREAMseq investigated the best sequence of care when you have multiple options.
About the DREAMseq Trial
The DREAMseq phase III, trial was conducted across 849 U.S. locations and was led by Michael Atkins, M.D. Professor at Georgetown Lombardi Comprehensive Cancer Center, on behalf of the ECOG-ACRIN Cancer Research Group and sponsored by the National Cancer Institute.
About 106,000 people were estimated to receive a new diagnosis of melanoma in 2021 and more than 7,000 were projected to die of the disease, according to the National Cancer Institute. While melanoma rates rose rapidly over the past few decades, the latest Annual Report to the Nation on the Status of Cancer noted that mortality rates are now declining—reflecting a significant increase in survival due to improved treatment options, among other factors.
The new study provides strong evidence demonstrating how best to treat patients with advanced melanoma that contains a mutation called BRAF V600E: immunotherapy is the better initial approach, even for people whose tumors have a mutation that could be treated by targeted therapies.
Starting in 2015, 265 patients with metastatic melanoma were randomly assigned to one of two groups. One group started treatment with combination immunotherapy (ipilimumab and nivolumab) and the second group started with the targeted therapies dabrafenib and trametinib. Ipilimumab and nivolumab, which are given intravenously, work by unleashing the breaks of the immune system to find and destroy cancer cells. Dabrafenib and trametinib are pills that, when given together, inhibit the function of the proteins associated with the BRAF mutation, leading to direct killing of tumor cells. Patients in each group could receive the other drug combination if the first treatment failed to control their cancer.
After two years, the clinical trial was stopped, with 59% of patients having been on the study. Two-year overall survival was 72% among patients who received combination immunotherapy first versus 52% for those who got the two targeted therapies as initial treatment. Progression-free survival, where the cancer remains stable or improves, also tended to be better for the immunotherapy group.