No Added Toxicity, But Some Unexpected Findings
The study was conducted in patients with early-stage, operable TNBC (with and without baseline FASN expression) and no prior PPI use within 12 months.
All patients started daily high-dose omeprazole 4 to 7 days prior to start of AC-T neoadjuvant chemotherapy (the addition of carboplatin was allowed per physician discretion) and continued until surgery.
The primary endpoint was pCR, defined as no residual invasive disease in breast or axilla, in patients with baseline FASN expression (FASN+). The pCR rate was 71.4% in the 28 FASN+ patients and 71.8% in all 42 enrolled patients. The researchers had targeted a pCR rate of 60% in the FASN+ patients. Also, among the subset of 15 patients who received carboplatin with AC-T, the pCR was 73%.
These two findings both have limitations, commented Dr. Berger. She pointed out that it is “unexplained” as to why the pCR rates were similar among the FASN+ patients and the total population (including 14 FASN– patients); the pCR rate would be expected to be lower in the total population, she suggested.
Further, it was also unexplained as to why there were similar pCR rates with or without carboplatin; other research has demonstrated improved pCR rates in patients receiving additional carboplatin (compared to AC-T alone) but at the cost of increased toxicity, she said.
Dr. Sardesai said that omeprazole was well tolerated with no known grade 3 or 4 toxicities and that the chemotherapy toxicity was similar to prior studies of AC-T. PPIs have side effects if taken for longer than a year, including a higher risk of infections, osteoporosis, and low magnesium, he also commented.
“Omeprazole can be safely administered in doses that inhibit FASN. The addition of high-dose omeprazole to neoadjuvant AC-T yields a promising pCR rate without adding toxicity,” the authors concluded in their abstract.
Dr. Sardesai also highlighted the fact that using a PPI for breast cancer is an example of drug repurposing. The approach offers a way of rapid drug development because PPIs have complete safety and pharmacokinetics data available, he said. “If we can prove the efficacy, the treatment can move forward quickly and be available in clinical practice much sooner than with traditional drug development.”
The study was funded by the Breast Cancer Research Foundation. Dr. Sardesai disclosed financial ties to Novartis and Immunomedics. Other study authors have ties to industry. Dr. Berger disclosed no relevant financial relationships.
This article first appeared on Medscape.com.