Filip Janku, MD of MD Anderson discusses Next generation BRAF inhibitor cancer drug shows promise in early patient trial.
In an early patient trial presented at the 32nd EORTC-NCI-AACR[1] Symposium on Molecular Targets and Cancer Therapeutics taking place online, a new drug intended to act on cancers with an altered BRAF gene has shown promise.
The BRAF gene is involved in telling healthy cells when to develop and shape new cells, but in many types of cancer, including types of bowel, brain, and skin cancer, it is also known to go wrong or mutate. In the treatment of patients, a few BRAF inhibitor drugs have already proven successful. These ‘first-generation’ BRAF inhibitors, however, do not function on all BRAF mutated cancers, and cancers become resistant to treatment in other cases.
The latest drug, PLX8394, is a BRAF inhibitor of the ‘next generation,’ intended to prevent this resistance and function against cancers with a broader range of BRAF mutations.
Dr. Filip Janku, Associate Professor for Investigational Cancer Therapeutics (Phase I Clinical Trials Program) and Center Medical Director for Clinical and Translational Research Center at the University of Texas MD Anderson Cancer Center in Houston, Texas, USA, presented the results of phase I / II trial at the Symposium.
To date, 75 patients in the study have been treated with the next generation BRAF inhibitor PLX8394, taken by mouth twice a day, with or without another medicine called cobicistat. Researchers were available to review data on 45 of these patients with BRAF alterations who obtained PLX8394 and cobicistat. These patients had advanced cancers and, prior to completing the study, most had already undergone three different forms of treatments.
The researchers reported that the addition of cobicistat resulted in the PLX8394 level in the blood doubling to tripling.
Ten of the 45 patients (22 percent) had a partial reaction to the new drug, indicating that at least 30 percent of their tumors shrank. This included three individuals with glioma (a type of brain tumor), two with cancer of the ovary, and others with cancer of the intestine, cancer of the thyroid, or melanoma (a type of cancer of the skin). Ten out of 45 patients stayed on medication for at least two years throughout the review of the results.
High levels of liver enzyme and bilirubin in the blood, suggesting a risk of liver injury, were significant side effects of treatment encountered by some patients; these levels decreased when PLX-8394 was stopped and the dosage was reduced. Diarrhoea was also encountered by some patients.
The combination of PLX8394 and cobicistat continues to be tested by Dr. Janku and his colleagues for the treatment of patients, in particular, to determine the optimal dosage of the drugs.
On behalf of the NCI, William R. Sellers, Professor of Medicine at the Dana-Farber Cancer Institute, Harvard Medical School, USA, is co-chair of the EORTC-NCI-AACR Symposium and did not participate in the study. He commented: “Understanding the genes in cancer go wrong and how they are mutated is a critical step towards discovering therapies for specific patients that are targeted to function effectively.” In nearly half of melanoma cases, as well as in smaller fractions of colorectal and lung cancer, BRAF is a mutated gene. Therefore, it is an effective therapeutic target and, indeed, in such patients, BRAF inhibitors have considerable clinical benefit.