May 20th, 2013

Biomarker Analysis Identifies Women Most Likely to Benefit From Kadcyla


Among women with metastatic, HER2-positive breast cancer, those with the highest tumor HER2 levels benefit the most from the drug Kadcyla™ (ado-trastuzumab emtansine, formerly known as T-DM1), according to the results of a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2013, held in Washington, D.C., April 6-10.

HER2 is a protein involved in normal cell growth. Approximately 20-25% of breast cancers overexpress (make too much of) the HER2 protein, and this over-expression contributes to cancer cell growth and survival. HER2-targeted therapies such as Herceptin have dramatically improved outcomes for women with HER2-positive breast cancer, but researchers continue to explore new approaches to treatment.

Kadcyla is part of a new class of drugs called antibody-drug conjugates, which consist of an antibody attached to a toxic chemotherapy. It combines Herceptin and a chemotherapy drug (emtansine or DM1) that interferes with cancer cell growth. Kadcyla delivers Herceptin and DM1 directly to HER2-positive cells, and limits exposure of the rest of the body to the chemotherapy.

The EMILIA study was a phase III clinical trial that led to FDA approval of Kadcyla. It showed that Kadcyla prolonged progression-free survival and overall survival for patients with HER2-positive metastatic breast cancer compared to Tykerb® (lapatinib) plus Xeloda® (capecitabine).

Among women with HER2-positive cancer, the degree of HER2 expression differs from patient to patient. Researchers performed a sub-analysis on the data from the EMILIA study to analyze tissue samples from patients in the study and examine whether tumor levels of HER2 as assessed by the amount of HER2 messenger ribonucleic acid (mRNA), affected treatment response. Patients with tumor samples expressing greater than the median amount of tumor HER2 mRNA were considered to have high levels of HER2. Those with tumor samples expressing the median amount of tumor HER2 mRNA or less were considered to have low levels of HER2.

The results of the analysis indicated that patients with tumor expressing higher levels of HER2 derived greater benefit from Kadcyla than those with tumors expressing lower levels of HER2. Overall survival was 34.1 months for patients with high levels of HER2 compared with 26.5 months for those with lower levels. Among patients with tumors expressing higher levels of HER2, those receiving Kadcyla had a 47 percent decreased risk of death compared with those receiving Tykerb/Xeloda.

What’s more, the researchers also evaluated whether tumor mutations in the PIK3CA gene affected treatment response because patients with this mutation typically do not respond as well to HER2-targeted therapies as their counterparts without the mutation. However, the analysis revealed that PIK3CA mutation status did not diminish treatment response.

The researchers concluded that women with the highest tumor HER2 levels benefit the most from the drug Kadcyla, regardless of PIK3CA mutation status. Measuring HER2 levels may help physicians individualize treatment among this population.


Baselga J, Verma S, Ro J, et al. Relationship between tumor biomarkers (BM) and efficacy in EMILIA, a phase III study of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC). Presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10. Abstract LB-63.

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Tags: Breast Cancer, Metastatic Breast Cancer, News, Uncategorized