Neal J. Meropol, MD, Chief of Hematology and Oncology at University Hospitals ­Seidman Cancer Center and Case Western Reserve University, Cleveland, discussed the study by Kothari et al presented at the Gastrointestinal Cancers Symposium. He noted that complex interactions exist between PIK3CA and other signaling pathways, including pathways for prostaglandin synthesis, and this contributes to the growth and development of colorectal cancer.

“So, the natural question is whether mutations in PIK3CA will influence the potential benefit from aspirin in patients with colorectal cancer,” he said. “Aspirin’s effects are not only on cell signaling. Aspirin also has myriad effects on the tumor microenvironment that may play a role in this context.”

All Available Data Limited

In contrast to previous studies with “very impressive hazard ratios” that support the underlying hypothesis, the Kothari study found no clear survival benefit for aspirin users with PI3KCA mutations,” Dr. Meropol suggested. But he pointed out that all available datasets are limited by challenges, including lack of randomization between aspirin use and no use, reliance on patient reports of aspirin use, variations in dosing of aspirin, variation in cancer stages, and small samples sizes.

“A prospective evaluation of aspirin and COX2 inhibition in the PIK3CA-mutated colorectal cancer population is definitely needed,” he said, predicting that “meaningful data” will emerge from ongoing randomized studies of aspirin and celecoxib (Celebrex) in the adjuvant setting. ■

Disclosure: Dr. Meropol has received consulting fees from Precision Therapeutics.