Combination of HER2-Targeted Therapies May Provide Breast Cancer Benefit

Posted on January 3rd, 2011 by

Among women with early, HER2-positive breast cancer, treatment with a combination of HER2-targeted therapies may produce better outcomes than treatment with only a single HER2-targeted therapy. This was the conclusion of two studies presented at the 2010 San Antonio Breast Cancer Symposium. One of the studies evaluated neoadjuvant (before surgery) Herceptin® (trastuzumab) plus Tykerb® (lapatinib), and the other evaluated neoadjuvant Herceptin plus pertuzumab.

Approximately 20-25% of breast cancers overexpress (make too much of) a protein known as HER2. Fortunately, the development of drugs that specifically target HER2-positive breast cancer has improved outcomes. These drugs include Herceptin, Tykerb, and the investigational drug pertuzumab.

Combinations of HER2-targeted therapies have shown a benefit in studies of women with metastatic breast cancer (cancer that has spread to other parts of the body), and researchers are also evaluating these combinations in women with earlier-stage breast cancer.

The NeoALTTO study is a Phase III clinical trial that has enrolled 455 women with early, HER2-positive breast cancer.[1] The study was restricted to women with operable breast cancer greater than 2 cm in size; women with inflammatory breast cancer were excluded. Study participants were assigned to one of three neoadjuvant (before surgery) treatment groups:

1)    Tykerb plus chemotherapy

2)    Herceptin plus chemotherapy

3)    Herceptin plus Tykerb plus chemotherapy

The primary outcome of the study was the pathological complete response (pCR) rate. A pCR refers to the disappearance of detectable cancer at the time of surgery. After surgery, patients received additional chemotherapy and HER2-targeted therapy.

  • Response rates were highest among women treated with the combination of Herceptin and Tykerb: a pCR was achieved by 51.3% of women in the combined Herceptin/Tykerb group, 29.5% of women in the Herceptin group, and 24.7% of women in the Tykerb group.

In a second study, a Phase II clinical trial known as NeoSphere, researchers enrolled 417 women with Stage II or Stage III HER2-positive breast cancer.[2] Study participants were assigned to one of four neoadjuvant treatment groups:

1)    Herceptin plus chemotherapy

2)    Herceptin plus pertuzumab plus chemotherapy

3)    Herceptin plus pertuzumab (without chemotherapy)

4)    Pertuzumab plus chemotherapy

After surgery, patients received additional chemotherapy and Herceptin.

  • Response rates were highest among women treated with the combination of Herceptin, pertuzumab, and chemotherapy. A pCR was achieved by 45.8% of women treated with all three drugs, 29% of women treated with Herceptin plus chemotherapy, 24% of women treated with pertuzumab plus chemotherapy, and 16.8% of women treated with Herceptin plus pertuzumab without chemotherapy.

Taken together, these studies suggest that a combination of HER2-targeted therapies may be most effective against HER2-positive breast cancer.

References:


[1] Baselga J, Bradbury I, Eidtmann H et al. First results of the NeoALTTO Trial (BIG 01-06/EGF 106903): A phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Presented at the 33rd annual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract S3-3.

[2] Gianni L, Pienkowski T, Im Y-H et al. Neoadjuvant pertuzumab (P) and trastuzumab (H): antitumor and safety analysis of a randomized phase II study (‘NeoSphere’). Presented at the 33rd annual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract S3-2.

Copyright © 2010 CancerConsultants Breast Cancer Information Center. All Rights Reserved.

Tags: Breast Cancer, News, Stages II-III Breast Cancer

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