Possibility of Precision Medicine

Ivette’s experience—and those of the other 121 patients included in the first published “basket” study1—illustrates the long-heralded promise of precision medicine.


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By selecting patients with BRAF V600 mutation–positive cancer independent of histopathology, the challenge of treating genetically heterogenous tumors can be skirted and patients such as Ivette, whose rare tumor type makes it unlikely she would ever have been enrolled in a clinical trial, can now be treated.

“Sequencing will help us find needles in the haystack, and there are so many needles lost in the haystack,” José Baselga, MD, PhD, the study’s senior author and MSK physician-in-chief and chief medical officer, told Cancer Therapy Advisor.

The BRAF V600 mutation is commonly found in patients with unresectable or metastatic melanoma, and it is for this indication that vemurafenib received U.S. Food and Drug Administration approval in August 2011. The agent causes apoptosis by inhibiting BRAF in melanoma cell lines with the V600 mutation.

MSK’s early phase 2 study was designed to test the effect of vemurafenib in patients with the BRAF V600 mutation with nonmelanoma cancers.

The protocol grouped 122 patients from 23 centers in France, Germany, Spain, the United Kingdom, and the United States in six cohorts—or “baskets”—by prespecified tumor types: non-small cell lung cancer (NSCLC), ovarian, colorectal, and breast cancers, cholangiocarcinoma, and multiple myeloma. The seventh basket housed all other tumor types that showed BRAF-mutation–positive disease.

Results of the study, published in The New England Journal of Medicine, demonstrated the preliminary clinical efficacy of vemurafenib in this diverse population.

The highest response rates—43% and 42%—were observed among patients with Erdheim-Chester disease, Langerhans’-cell histiocytosis, and NSCLC, respectively. In addition, anecdotal responses were observed “in patients with salivary-duct cancer, clear-cell sarcoma, low-grade serous ovarian cancer, glioblastoma, anaplastic ependymoma, pancreatic cancer, and carcinoma of unknown primary type,” the study noted.

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“The beauty of a basket trial is that it allows you to be incredibly flexible so that you can learn as you move along,” Dr. Baselga told Cancer Therapy Advisor.

For example, just when the basket study’s colorectal cancer cohort was about to close due to inactivity, two papers were published, one in Nature and one in Cancer Discovery, showing that adding cetuximab to vemurafenib better inhibited BRAF.