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Letrozole–lapatinib combination did not improve outcomes in HR-positive, HER-2–negative breast cancer
The addition of lapatinib to letrozole did not significantly improve response rates in women with HR-positive, HER-2–negative operable breast cancer, according to results of a phase 2b study.
However, patients with PIK3CA mutations were more likely to respond to treatment with letrozole plus lapatinib (Tykerb, GlaxoSmithKline) than letrozole plus placebo.
The analysis included 92 postmenopausal women with stage II to IIIA primary breast cancer (median age, 70 years). Researchers randomly assigned 43 patients 2.5 mg daily letrozole plus 1,500 mg daily lapatinib. The other 49 patients received letrozole plus placebo. The preoperative therapy continued for 6 months, and patients underwent surgery within 2 weeks from the last dosage.
Overall, 70% of women in the lapatinib arm achieved a response, a rate that was not significantly different from the 63% response rate in the placebo arm.
Patients in both arms demonstrated significant decreases in Ki-67 and pAKT expression.
Skin disorders, diarrhea and liver function test abnormalities were more common among women assigned lapatinib; however, researchers noted most adverse events were mild. One patient in the lapatinib arm experienced grade 4 skin toxicity.
Additional biomarker analyses indicated 34 patients (37%) harbored PIK3CA exon 9 or 20 mutations. Among women assigned lapatinib, 93% of those with mutated PIK3CA responded to treatment vs. 63% of those with wild-type PIK3CA (P=.04).
“Our study demonstrated that, in HR-positive/HER-2–negative patients, letrozole–lapatinib and letrozole–placebo resulted in a similar clinical response rate and similar effects on Ki-67 and pAKT,” the researchers concluded. “Our secondary endpoint findings of a significant correlation between PIK3CA mutation and response to letrozole–lapatinib in HR-positive/HER-2–negative early breast cancer must now be independently confirmed.”
Disclosure: The researchers report employment/leadership positions or consultant/advisory roles with, stock ownership in and honoraria/research funding from GlaxoSmithKline.