Lapatinib Plus Letrozole May Improve Efficacy

In metastatic breast cancer (MBC), lapatinib (Tykerb) + letrozole(Drug information on letrozole) (Femara) delayed disease progression in HER2+, HR+ patients, according to initial results from a phase III trial (EGF30008) presented by Stephen Johnston, MD (abstract 46).

EGF30008 is testing whether combined endocrine and targeted HER2 inhibition improves outcomes in HR+ MBC. Crosstalk between the EGFR and steroid receptor pathways has been implicated in endocrine resistance in breast cancer. For HR+ patients receiving AIs, adding a drug that targets both EGFR and HER2 pathways may enhance endocrine responsiveness, Dr. Johnson said. “This study suggests that combining an AI with the orally active dual TKI lapatinib may be a better approach.”

Patients (N = 1,286) received letrozole ± lapatinib as first-line treatment. In the cohort with HR+, HER2+ disease (n = 219), lapatinib/letrozole significantly increased median PFS from 3.0 mo with letrozole alone to 8.2 mo, for a 29% reduction in risk of progression (P = .019). Response rates were significantly increased (15% to 28%) and clinical benefit was observed in 29% and 48%, respectively; OS is premature, but a nonsignificant 26% reduction in risk was seen with the combination.

In the entire population (irrespective of HER2 status), there was less effect with the combination, though the 1-mo increase in PFS (11.9 vs 10.8 mo) was statistically significant (P = .026). In HER2- patients, median PFS was ~ 13.5 mo in both arms; no additional benefit was seen with lapatinib. When HER2- patients were stratified by endocrine sensitivity, endocrine-resistant patients (relapse < 6 mo post-tamoxifen) had improvement in PFS from 3.1 mo with letrozole to 8.3 mo with both agents: a 22% nonsignificant risk reduction. For endocrine- sensitive patients, median PFS was ~ 15 mo in each arm. Dr. Johnston called these findings intriguing but cautioned that at this point they are exploratory only.