Monday, August 24, 2015

BRAF V600 Is Targetable in Some Nonmelanoma Cancers

“Efforts by the Cancer Genome Atlas and other initiatives to characterize the genetic landscape of most tumor types have identified BRAF V600 mutations in nonmelanoma cancers, including colorectal cancer, NSCLC, papillary thyroid cancer, diffuse gliomas, cholangiocarcinoma, hairy-cell leukemia, multiple myeloma, Langerhans’-cell histiocytosis and Erdheim-Chester disease”.
In the cancer types with less response, Hyman noted, the BRAF V600 mutation is typically present in fewer than 5 percent of tumors that have resisted conventional therapy and spread, so only those patients would be candidates for the drug.

But the so-called “basket” study from South San Francisco-based Genentech (NYSE: DNA) and its Swiss parent, Roche (SWX: RO), is significant because it is the first completed clinical trial lumping together several genetically similar cancers. Conducted by researchers at the Memorial Sloan Kettering Cancer Center, phase 2 results from a basket trial evaluated the effect of vemurafenib on nonmelanoma BRaf V600-mutated cancers in 122 patients across 23 global centers.

One patient in the study, MaryAnn Anselmo, had been diagnosed with stage 4 glioblastoma in 2013.
Patients with colorectal cancer received oral vemurafenib (960 mg twice daily) alone (n = 10) or with IV cetuximab (Erbitux; Bristol-Myers Squibb, Lilly) at a loading dose of 400 mg/m, followed by a weekly 250-mg/m dose (n = 27). That gene makes a protein that directs cell growth but is mutated in certain cancer patients. “Not only did 40 percent meet strict criteria for response, but almost all of them had improvement in their symptoms and no one progressed while receiving the medicine”, said Dr. Hyman. Secondary endpoints included PFS, OS, duration of response and safety. According to the data, the non-small-cell lung cancer cohort had a response rate of 42%, with a median progression-free survival time of 7.3 months.

The goal was to see if the drug vemurafenib, already approved for metastatic melanoma cases with the BRAF mutation, would work in other tumors with the same mutation.
Forty-three percent (95% CI, 18-71) of patients with ECD or LCH achieved a response. Patients were enrolled in six prespecified cancer cohorts, and patients with all other tumor types were enrolled in the seventh cohort.

In the new study, researchers focused on a mutation known as BRAF V600, which is a defect in a genetic instruction that tells a cell when to die. “We have proven that histology-independent, biomarker-selected basket studies are feasible and can serve as a tool for developing molecularly targeted cancer therapy”, said Dr. Baselga, the study’s senior author. “Confirmation of promising activity identified in basket studies will often necessitate additional studies”.
The study was funded by F. Hoffmann-La Roche/Genentech.
Overall Hyeman stays optimistic about the study’s findings.

No comments: