The US Food and Drug Administration (FDA) announced that it has approved the drug vemurafenib for the treatment of patients with BRAF V600-mutant Erdheim-Chester disease (ECD). This is the first approval of a targeted therapy based on a basket study and the first-ever drug approved for ECD, a rare blood disorder.

This landmark approval came as a direct result of research at Memorial Sloan Kettering Cancer Center (MSK). MSK researchers, led by Physician-in-Chief José Baselga, MD, PhD, pioneered the concept of a basket study, which harnesses the power of precision medicine by assigning treatments to patients based on the genetic alterations driving their cancers rather than where their tumors originated in the body. This approval is based off of the data of 22 ECD patients enrolled in the phase 2 VE-BASKET study.

“This approval marks a new era in targeted cancer treatment as we expect this to be the first of many approvals based on precision medicine clinical trials,” said Dr. Baselga. “At MSK, we have long seen the promise of genome-driven oncology and histology-independent basket studies and this approval validates this important work. The FDA’s ruling provides hope not just to patients with ECD, but also to others who may benefit from targeted therapies.”

“This unique clinical trial design allows us to broaden eligibility and treat patients with diseases that have historically been underrepresented or even entirely absent in clinical trials, such as ECD,” explained David Hyman, MD, Chief of the Early Drug Development Service at MSK. “While this approval is an important step, we believe this is just the beginning, as we have already seen precision medicine benefit many of the patients treated on these basket studies.”

ECD is one of an extremely rare form of blood cancers known collectively as histiocytoses that can lead to life-threatening complications, including damage to the heart, lungs, and kidneys. It’s estimated that there are fewer than 300 cases of ECD in the United States. More than 50% of people with ECD have BRAF V600-mutant disease, indicating that they would benefit from this drug. Previous treatments for ECD have included off-label use of chemotherapy, radiation, steroids, and the immunotherapy drug interferon, but all of these have limited efficacy based on anecdotal reports and potentially severe side effects.

Based on the work of MSK medical oncologist Paul Chapman, MD, vemurafenib was previously approved for the treatment of advanced melanoma that carries the BRAF V600E mutation. Dr. Chapman led the phase 3 trial for vemurafenib that led to the drug’s approval for that disease in 2011. In August 2017, vemurafenib was granted FDA Priority Review and Breakthrough Therapy Designation for the treatment of BRAF V600-mutant ECD.

This approval is based on data from the phase 2 VE-BASKET study, a nonrandomized, histology-independent evaluation of the efficacy of vemurafenib, an inhibitor of BRAF V600 kinase, in non-melanoma cancers, including ECD. This first-in-kind study enrolled participants across multiple diseases, based predominantly on genetic profile rather than where the cancer originated. Initial study results were published in the New England Journal of Medicine in August 2015.

Final results for the 22 people with ECD showed a best overall response rate of 54.4% by RECIST v1.1. Importantly, responses and disease control were extremely durable. The median duration of response was not estimable at a median follow-up time of 26.6 months. At two years, 83% of patients remained progression free. The safety of vemurafenib in ECD patients was similar to that previously reported in patients with melanoma. The most common adverse events were joint pain, rash, hair loss, fatigue, change in heart rhythm, and skin tags.