New results from three clinical trials illustrate the evolving treatment options for women with HER2-positive breast cancer. HER2-positive breast cancers produce too much HER2 receptor protein, are particularly aggressive, and account for almost 20% of all breast cancer diagnoses.

One trial found improved overall survival with the investigational drug T-DM1 in women with advanced HER2-positive disease who had previously been treated with trastuzumab and taxane chemotherapy. The women treated with T-DM1 had better overall survival of 30.9 months than those treated with capecitabine and the HER2-targeted drug lapatinib (25.1 months). T-DM1 is an antibody-drug conjugate that combines trastuzumab, a monoclonal antibody, with the chemotherapy drug DM1.

“Only a few studies in metastatic breast cancer have shown an improvement in overall survival. It’s tough to do,” said the trial’s lead investigator, Dr. Sunil Verma of the Sunnybrook Odette Cancer Centre in Toronto. “The gain that we saw in this trial, an incremental improvement of 5.8 months, is one of the largest seen of any trial reported to date [in this disease]. And we’re seeing that gain with less toxicity.” The updated findings from the EMILIA trial were published in the New England Journal of Medicine (2012; doi: 10.1056/NEJMoa1209124).

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Two other clinical trials, HERA and PHARE, provided more evidence that the existing duration of adjuvant treatment with trastuzumab in women with early-stage breast cancer should remain 1 year.

The 5,000-patient HERA trial compared women receiving 2 years of adjuvant treatment with trastuzumab, 1 year of trastuzumab, or observation. After a median follow-up of more than 8 years, the progression-free and overall survival rates were nearly identical in the 1-year and 2-year treatment groups. The women who received 1 year of trastuzumab lived 24% longer without their disease progressing than the women who underwent observation.

The PHARE trial, involving 3,380 patients, compared 12 versus 6 months of adjuvant treatment with trastuzumab in the same patient population. This noninferiority trial sought to demonstrate that both treatment periods are essentially equivalent. After about 3.5 years of follow-up, the results are inconclusive for noninferiority between 6 and 12 months of adjuvant trastuzumab, though there was a strong trend favoring 12 months of treatment.

The shorter duration of treatment in the PHARE trial appeared to be safer, as the percentage of women who experienced cardiac events was nearly three times higher in women who received trastuzumab for 1 year (5.7% vs 1.9%). Notably, this trial considered a “cardiac event” as a composite variable that encompassed several heart-related problems, so data on cardiac events is difficult to interpret.

The lead investigators of both the HERA and PHARE trials, which were recently presented at the European Society for Medical Oncology Congress, agreed the standard of care for adjuvant treatment with trastuzumab in women with early-stage HER2-positive breast cancer should remain 1 year. Other international trials are also testing shorter durations of adjuvant trastuzumab treatment for women with early-stage HER2-positive breast cancer.