Charles L. Sawyers, MD
Charles L. Sawyers, MD, of Memorial Sloan Kettering Cancer Center, New York, commented on the SWOG S1320 study presented at the 2020 American Association for Cancer Research Virtual Annual Meeting.
“Intermittent therapy is standard with chemotherapy due to toxicity, but targeted therapies alleviate toxicities associated with chemotherapy and can provide continuous coverage,” he told listeners. “However, resistant cells may have reduced fitness, and continuous selective pressure allows subclones to evolve. Many times, these clones are less fit, which leads to the idea of giving intermittent therapy so that drug-sensitive cells can regrow.”
Dr. Sawyers continued, “The study in the abstract at hand was based on two papers in Nature and Cancer Cell, both converging on the conclusion that continuous dosing leads to greater resistance.” He suggested several potential explanations for the unanticipated findings, such as patient selection and use of a MEK inhibitor with a prolonged half-life that precluded a rapid drop in drug concentration, but none of them can be proven.
DISCLOSURE: Dr. Sawyers reported financial relationships with Novartis, Nextech, KSQ Therapeutics, Petra, and PMV Pharma.
Continuous dosing with dabrafenib and trametinib improved progression-free survival in patients with BRAF-mutated advanced melanoma compared with an intermittent-dosing strategy, according to results of the phase II SWOG S1320 randomized trial reported at the opening Plenary Session of the 2020...