Letrozole–dasatinib combo shows promise in ER+, HER2– metastatic breast cancer

The combination of the aromatase inhibitor (AI) letrozole plus the Src kinase inhibitor dasatinib appears to be well tolerated and effective, with a clinical benefit rate (CBR) of 71 percent in a cohort of postmenopausal patients with ER-positive, HER2-negative metastatic breast cancer (MBC), according to the results of a noncomparative phase II trial.

The trial randomized 120 patients with 0–1 prior chemotherapy and no previous AI exposure for MBC to receive either letrozole (2.5 mg/day orally; n=63) alone or with dasatinib (100 mg/day orally; n=57). Patients with disease progression on letrozole alone were allowed to crossover to dasatinib plus continued letrozole.

The primary endpoint of clinical-benefit-rate (CBR; complete response plus partial response plus stable disease ≥6 months) with the combination was 71 percent (95 percent confidence interval [CI], 58–83), exceeding the projected rate of 56 percent.

Similarly, the CBR rate of 66 percent (95 percent CI, 52–77) with letrozole alone surpassed the projected 39 percent rate.

In the crossover arm of the combination therapy in patients progressing on letrozole alone, the CBR was 23 percent. Median progression-free survival was higher with the combination than with letrozole monotherapy (20.1 vs 9.9 months).

Letrozole plus dasatinib was well tolerated despite the need to reduce dasatinib dose in 26 percent of patients.

The present data are encouraging and suggest that dasatinib may inhibit the occurrence of acquired resistance to AI therapy, researchers said.