SAN ANTONIO—Extending the duration of dual anti-HER2 therapy without chemotherapy did not significantly improve molecular response rates in HER2-positive (HER2+) breast tumors, according to findings of a randomized multicenter phase 2 neoadjuvant trial presented at the 2014 San Antonio Breast Cancer Symposium.

The trial “did not meet its primary endpoint of increasing pathologic complete response (pCR) to 45%,” reported lead study author Mothaffar F. Rimawi, MD, of the Baylor College of Medicine in Houston, TX. “This was mainly due to lower than expected pCR in both arms.

However, our study demonstrated two-fold numeric increases in pCR in the 24 weeks arm over the 12 weeks arm, and that increase was more than three-fold in the estrogen receptor-positive (ER+) subgroup.”

The study authors had hypothesized that in HER2+ breast cancer, longer treatment with anti-HER2 therapy (and endocrine therapy, if tumors are also ER+) would improve pCR rates. To test the hypothesis, they enrolled patients with HER2+ breast cancer to receive lapatinib plus trastuzumab (and estrogen deprivation therapy in patients with ER+ tumors) for 12 or 24 weeks, with biopsies at baseline and after 12 and 24 weeks.

Participants were enrolled between November 2011 and November 2013. A total of 94 patients were randomly assigned 2:1 to 12- or 24-week treatment regimens (33 patients and 61 patients, respectively).

pCR overall was 12% in the 12-week arm and 28% in the 24-week arm. Among ER+ patients, pCR rates were 9% and 33% for the 12- and 24-week arms, respectively, whereas pCR rates were similar among ER-negative patients in the two study arms (20% and 18%, respectively).

Adverse events were few and included elevated liver function tests (liver function: 0 in the 12-week arm vs. 9% of patients in the 24-week arm); diarrhea and mucositis (2% each in the 24-week arm only); and anemia and renal calculi (3% each in the 12-week arm only).There were no grade 4 toxicities.

“This is the first trial to show that longer treatment with dual anti-HER2 therapy in combination with an endocrine therapy, and without chemotherapy, leads to a meaningful increase in pCR rate in ER+/HER2+ breast cancer,” Dr. Rimawi concluded. “Targeted therapy without chemotherapy may offer a promising treatment strategy to patients with ER+/HER2+ breast cancer, and warrants further study.”


  1. Rimawi MF, Niravath PA, Wang T, et al. S6-02. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX.