MicroRNA May Predict Response to Bevacizumab

John K. Chan, MD

The results of a small clinical trial showed that low-level expression of a microRNA correlated with improved progression-free survival (PFS) in women with advanced ovarian cancer treated with chemotherapy plus the angiogenesis inhibitor bevacizumab.

Patients with low microRNA-378 (miR-378) expression had a median PFS of 9.2 months, more than double the 4.2-month PFS among patients with normal miR-378 expression (P = .035). No patient with normal miR-378 expression survived progression-free for as long as 6 months, said John K. Chan, MD, at the recent Society of Gynecologic Oncologists meeting in Orlando, Florida.

“Our data suggest that miR-378 is associated with treatment response after bevacizumab and chemotherapy in recurrent ovarian cancer,” said Chan, an oncologist at the University of California, San Francisco. “Differential microRNA expression may have clinical utility in determining response to novel therapeutics.”

MicroRNA is noncoding, singlestranded RNA involved in the regulation of gene expression. Some studies have suggested that microRNA expression may predict response to chemotherapy and influence cancer survival. However, no studies had examined associations between microRNA expression and biologic therapy, said Chan.

Using clinical and genetic information from the National Institutes of Health’s Cancer Genome Atlas, investigators identified 34 patients with recurrent serous ovarian cancer treated with chemotherapy and bevacizumab at recurrence. A search of the 800 microRNAs in the atlas revealed 33 that exhibited at least a twofold differential expression in tumors versus normal tissue from the same patient. The list of candidate microRNAs was subsequently whittled down to 5.

Comparing expression of the 5 microRNAs with clinical data, Chan and colleagues found that miR-378 expression had the strongest association with response to bevacizumab. Six of 10 patients with low-level expression had a progression-free interval of at least 6 months, compared with none of the 24 patients with normal miR-378 expression (P <.001).

Additional analyses showed that miR-378 expression was specific to bevacizumab and PFS. Differential expression of the microRNA did not predict response to chemotherapy or overall survival. In a multivariate analysis, only 2 factors remained significant as predictors of response to bevacizumab: the treatment-free interval of the last therapy before bevacizumab (P = .03) and miR-378 expression (P = .02).

Chan said that future studies will include examination of miR-378 gene targets that might influence response to bevacizumab. The microRNA is thought to affect expression of several genes involved in tumor angiogenesis.