Published in the New England Journal of Medicine, and reported in Drug Discovery & Development, the early phase 2 study, led by MSK Physician-in-Chief and Chief Medical Officer José Baselga, MD, PhD, looked at the effect of vemurafenib (Zelboraf) in multiple nonmelanoma BRAFV600-mutated cancers in 122 patients from 23 centers around the world. Vemurafenib had been proven to treat BRAFV600-mutated melanoma. People with lung, colorectal, and ovarian cancers were among those included in the study, as well as people with rare diseases, such as Erdheim-Chester disease. Previously, the efficacy of vemurafenib in nonmelanoma cancers remained unexplored, despite significant therapeutic potential.
According to Dr. Baselga, the study's senior author, "This study is the first deliverable of precision medicine. We have proven that histology-independent, biomarker-selected basket studies are feasible and can serve as a tool for developing molecularly targeted cancer therapy. While we can — and should — be cautiously optimistic, this is what the future of precision medicine looks like."
Basket studies enable the detection of early activity signals across multiple tumor types simultaneously, while offering the possibility that tumor lineage could influence drug sensitivity. The first study to follow this model, it explores treatment responses among tumors based on their mutation types and identifies promising signals of activity in individual tumor types that could be pursued in later studies. The results could guide researchers in finding different drug targets or developing therapies that combine vemurafenib with complementary treatments. Additionally, basket studies can increase the number of patients eligible to receive certain drugs. The mixed efficacy demonstrated in this study shows that drugs can reach patients beyond the current approved use while not working for everyone. Researchers concluded that the results demonstrate the potential benefits of basket studies and the need for more work to be done with these types of trials.
As explained by David Hyman, M.D., the study's first author and acting Director of Developmental Therapeutics at MSK "This kind of study is a beneficial way to do rare tumor research because it allows us to open the study to patients with diseases that are completely underrepresented in clinical trials in general, such as anaplastic thyroid cancer and glioblastoma,". "By broadening eligibility, we are translating potential benefits to as large a patient population as possible."
This clinical trial is the first in an impending wave of such studies focused on cancer-related mutations identified through the huge amounts of genomic data generated in recent years. It highlights the importance of further investigation into precision medicine, the researchers concluded.