Personalized medicine or PM is a medical model that proposes the customization of healthcare – with medical decisions, practices, and/or products being tailored to the individual patient. One of the main goals of personalized medicine is the ability to quickly and accurately determine the genetic background of a patient and prescribe the appropriate therapy based on their mutational signature. To address this vital component of modern medicine initiatives, researchers have designed a new form of clinical trial, dubbed a basket study, which explores responses to drugs based on the specific mutations in patients’ tumors rather than where their cancer originated.
Now, clinical researchers from Memorial Sloan Kettering Cancer Center (MSK) have published results from an early Phase II study that looked at the effect of the drug vemurafenib in multiple nonmelanoma BRAF V600-mutated cancers from a 122 patients in 23 centers around the world. Vemurafenib has been shown previously to be effective at treating BRAF V600-mutated melanoma, but this is the first report of the compound being used to treat nonmelanoma cancers such as lung, colorectal, and ovarian.
“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,” explained senior study author José Baselga, M.D., Ph.D., Physician-in-Chief and Chief Medical Officer at MSK. “While we can—and should—be cautiously optimistic, this is what the future of precision medicine looks like.”
The findings from this study were published recently in the New England Journal of Medicine through an article entitled “Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations.”
Basket studies allow for the detection multiple tumor types simultaneously, while permitting for the possibility that a specific tumor lineage might influence drug sensitivity. The current study is the first to follow this model and aims to explore treatment responses among tumors based on their mutation types and to identify promising signals of activity in individual tumor types that could be pursued in subsequent studies. Ultimately, the results should guide researchers to look at different drug targets or develop new combination therapies that combine with vemurafenib with complementary treatments.
In this study the investigators found that of the 122 participants, clinical activity was observed in a variety of tumor types such as non-small cell lung cancer, Erdheim-Chester disease, and Langherhans cell histiocytosis. Response rate and median progression-free survival in non-small cell lung cancer was 42% and 7.3 months, respectively. In Erdheim-Chester disease and Langherhans cell histiocytosis, the response rate was 43%—despite median treatment duration of 5.9 months, no patients progressed during therapy.
“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,” stated David Hyman, M.D., the study’s lead author and acting director of developmental therapeutics at MSK. “By broadening eligibility, we are translating potential benefits to as large a patient population as possible.”
The authors were excited by their findings and noted that this study was the first part of an imminent flood of such studies focused on cancer-related mutations identified through the huge amounts of genomic data generated over the past several years.
“We now have the landscape of all the most frequent cancer-causing mutations in the majority of tumor types, and we know there are a number of genes that are frequently mutated in some tumors and less frequently in others,” Dr. Baselga noted. “The next step is exploring appropriate drug combinations, knowing that these cells have a finite number of pathways.”
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