'Optimistic' Longer-term Outcomes for Metastatic Melanoma

This transcript has been edited for clarity.

Hello. I'm Dr Jeffrey Weber, a medical oncologist and deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University Langone Health in New York City. Today I would like to briefly discuss with you two trials recently published in the Journal of Clinical Oncology relating to long-term outcomes associated with targeted therapy or immunotherapy for melanoma.

COMBI-AD is a randomized, large, phase 3, well-powered adjuvant trial which tested the targeted therapies dabrafenib and trametinib versus placebo in high-risk resected stage IIIA, IIIB, and IIIC melanoma (per American Joint Committee on Cancer 7th edition criteria). Initial results were published after about 3 years of follow-up in late 2017 at the European Society for Medical Oncology meeting.^[1]

Recently, Hauschild and colleagues^[2]described the 4-year follow-up (median, 44 months) of the COMBI-AD trial. Four-year relapse-free survival (RFS) was approximately 54% versus 38% for placebo (hazard ratio [HR], 0.49). There appeared to be a plateau on the survival and RFS curves. Distant metastasis-free survival, a surrogate for overall survival, had an HR of 0.53 which matched RFS. Using estimated cure rate, they determined that about 54% of patients treated with dabrafenib and trametinib were probably cured versus about 38% of those who received placebo. A forest plot for RFS for dabrafenib and trametinib versus placebo looking at virtually every prognostic factor (eg, gender, age, macrometastases, micrometastases, ulceration, tumor burden, substage) found that the HRs did not overlap 1, and they were all in favor of dabrafenib and trametinib. This study certainly suggests longer-term benefit with the targeted therapies dabrafenib and trametinib for adjuvant therapy of resected high-risk stage III melanoma.