In the era of precision medicine, targeting the mutations driving cancer growth, rather than the tumor site itself, continues to be a successful approach for some patients. In the latest example, researchers from Penn Medicine and other institutions found that treating metastatic thyroid cancer patients harboring a BRAF mutation with the targeted therapy vemurafenib —originally approved for melanoma patients with the mutation—showed promising anti-tumor activity in a third of patients.  The results were published in this week’s Lancet Oncology.

The phase II clinical study included results from 51 patients enrolled at 10 centers around the world with progressive, radioactive iodine-refractory (RAI) papillary thyroid cancer and a BRAF mutation who were no longer responding to prior therapies. After a 15-month follow up, 16 patients from two cohorts had partial responses, with an overall response rate of 38 and 27 percent in each of the cohorts.

“For this group of patients, who have little to no options, that’s a significant improvement,” said Marcia Brose, MD, PhD, an associate professor of Otorhinolaryngology: Head and Neck Surgery and Hematology/Oncology and director of theCenter for Rare Cancers and Personalized Therapy and Penn’s Abramson Cancer Center. “This promising clinical trial is the next step in a series of trials to identify new drugs that are fundamentally shifting the horizon – improving the outcome for patients with advanced differentiated thyroid cancer.”

About 62,450 people were diagnosed with differentiated thyroid cancer in 2015. BRAF mutations, which occur in about 40 to 50 percent of these patients, have been associated with aggressive tumors and decreased ability of tumors to respond to radioactive iodine, typically the first line of treatment in these patients.  Patients are often cured by surgery, without or without RAI, but 50 percent of them with residual, recurrent or metastatic ultimately do not respond, and another avenue is needed.

Vemurafenib joins other multi-targeted kinase inhibitors (MKIs) (sorafenib, lenvatinib) shown to be effective in this patient population; in spite of responses to these drugs, the responses are temporary and additional treatment options are needed.

For the study, researchers enrolled a total of 51 patients between January 2011 and January 2013. Patients in cohort one (26 patients) had not been previously treated with MKIs, while patients in cohort (25) were treated with MKIs. Some in both groups had previously been treated with chemotherapy as well.

In cohort one, 10 patients had a partial response to vemurafenib, and an additional nine achieved stable disease for at least six months, for a combined disease control rate of 73 percent. The median progression free survival was 18.2 months.

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