Innovative Cancer Study Design Yields Important Insights

A new form of clinical trial design called a “basket study” enables the detection of early signals of activity across multiple tumor types simultaneously, while allowing for the possibility that tumor lineage might influence drug sensitivity.  Memorial Sloan Kettering Cancer Center (New York, USA) researchers employed this new design 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.  Specifically, the team studied vemurafenib (Zelboraf) in multiple nonmelanoma BRAFV600-mutated cancers in 122 patients from 23 centers around the world. Vemurafenib previously has 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. The findings illustrate the preliminary clinical efficacy of vemurafenib in multiple nonmelanoma BRAFV600-mutated cancers. Of the 122 trial participants, clinical activity was observed in various tumor types. Preliminary vemurafenib activity was observed in non-small cell lung cancer as well as Erdheim-Chester disease and Langherhans cell histiocytosis. Response rate and median progression-free survival in non-small cell lung cancer was 42 percent and 7.3 months, respectively. In Erdheim-Chester disease and Langherhans cell histiocytosis, response rate was 43 percent; despite median treatment duration of 5.9 months, no patients progressed during therapy. Anecdotal responses were seen in anaplastic pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary duct cancer, ovarian cancer, clear cell sarcoma, and colorectal cancer (cetuximab combination only).  Observing that: “The histologic context is an important determinant of response in BRAF V600-mutated cancers,” the study authors are hopeful that their results will ultimately guide researchers in looking for different drug targets or developing therapies that combine vemurafenib with complementary treatments.