We believe that PI3K-alpha inhibitors may be even better than pan-PI3K inhibitors.
—Carlos L. Arteaga, MD
Carlos L. Arteaga, MD, the Donna S. Hall Chair in Breast Cancer Research and Director of the Center for Cancer Targeted Therapies at Vanderbilt University School of Medicine, Nashville, commented on the BELLE-2 trial for The ASCO Post.
“We have learned that there is a subgroup of patients, who are identifiable with a blood test, that may benefit from this class of drugs, several of which are in development. The pan-PI3K inhibitor buparlisib inhibits all PI3K molecules—alpha, beta, gamma, delta. Of these, the main offender in breast cancer is the alpha type, which is frequently mutated and, as a result, is overactivated,” he explained.
“Because of this, we believe that PI3K-alpha inhibitors may be even better than pan-PI3K inhibitors,” he added.
Since these would not inhibit all PI3K molecules, they may be less toxic and better tolerated. This is very important with long-term therapy. Whether response rates would be higher with PI3K alpha-specific more specific inhibitors is not yet clear, said Dr. Arteaga. “But what we are seeing so far is encouraging,” he commented.
He added, however, that the pan-PI3K inhibitors may have most value against tumors where other PI3K molecules are cancer drivers.
More on Circulating Tumor DNA
Dr. Arteaga further commented on using circulating tumor DNA to detect mutations, which he said would be particularly useful for clinical trial enrollment, particularly in patients where a tumor biopsy is not doable and/or safe.
“Beware, though,” he added, “that the blood test does not detect the whole universe of alterations that could still be detected in a tissue biopsy.” ■
Disclosure: Dr. Arteaga reported no potential conflicts of interest.
Addition of the oral investigational pan-PI3K inhibitor buparlisib to the endocrine agent fulvestrant (Faslodex) improved progression-free survival among postmenopausal women with advanced hormone receptor–positive/HER2-negative advanced breast cancer.
“We are happy to announce that the phase III...