Combination of HER2-Targeted Therapies May Provide Breast Cancer Benefit

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) HerceptinR (trastuzumab) plus TykerbR (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.[i] 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:

Tykerb plus chemotherapyHerceptin plus chemotherapyHerceptin 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.[ii] Study participants were assigned to one of four neoadjuvant treatment groups:

Herceptin plus chemotherapyHerceptin plus pertuzumab plus chemotherapyHerceptin plus pertuzumab (without chemotherapy)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.? While these data are very encouraging, both studies were small and we do not know that the improvement in pCR will result in fewer recurrences or longer survival.? At this point, these studies should stimulate additional research, but they should not be used as evidence to change clinical practice standards.

[i] 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.

[ii] 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.

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