A randomized clinical trial offers evidence that a combination of two targeted melanoma drugs, when given continuously, improves progression-free survival when compared with intermittent treatment, according to study results presented by Algazi et al at the American Association for Cancer Research (AACR) Virtual Annual Meeting (Abstract CT013).
The study, SWOG S1320, focused on treatment for patients with melanoma and mutations in the BRAF gene—specifically, BRAF V600E and BRAF V600K mutations.
The research team enrolled 249 eligible patients from 68 clinical sites over a 5-year period. Of the 249 patients, 206 were randomly assigned—105 to continuous treatment and 101 to intermittent treatment. Every patient was given the commonly prescribed BRAF and MEK inhibitor combination regimen of dabrafenib and trametinib. One group of patients took the combination each day until their cancer progressed. Another group took the same daily combination on a 3-week-off, 5-week-on schedule until their cancer progressed. During the treatment period, each patient had a computed tomography scan every 8 weeks to measure their tumor size. Patients also gave blood and tumor samples.
Results showed that median progression-free survival was 9.0 months among patients who received continuous drug doses and 5.5 months among patients who received intermittent dose.
There was no difference in overall survival between groups (median overall survival = 29.2 months in both arms, P = .93) at a median follow-up of 2 years. Seventy-seven percent of patients treated continuously discontinued treatment due to disease progression vs 84% treated intermittently.
Why continuous treatment proved more effective isn’t clear, although researchers said the tissue and blood samples taken during the trial may hold clues and can be used for further study. About half of the patients who participated in the trial have died over the course of the study, which continues to follow those who are still alive.
Antoni Ribas, MD, PhD, is the senior leader of the trial, the former Chair of the Melanoma Research Committee at SWOG, and AACR President. He is also a Professor of Medicine at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA); Director of the UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program, and Director of the Parker Institute for Cancer Immunotherapy Center at UCLA.
Antoni Ribas, MD, PhD
“The idea of prescribing therapy intermittently made sense,” said Dr. Ribas. “Cancer cells wouldn’t have enough time to get used to it and become resistant—a notion that was supported scientifically by well-conducted studies in the laboratory. This clinical study illustrates the importance of ultimately testing hypotheses in human patients.”
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