Herceptin Given At Same Time As Chemotherapy May Provide Most Benefit for Breast Cancer

The results of a Phase III clinical trial suggest that starting HerceptinR (trastuzumab) during chemotherapy for early-stage, HER2-positive breast cancer may be more effective than starting Herceptin after chemotherapy has been completed. These results were published in the Journal of Clinical Oncology.????

Fifteen to 20 percent of?breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells and a worse breast cancer prognosis. Fortunately, the development of drugs such as Herceptin that specifically target HER2-positive cells has improved prognosis for women with HER2-targeted breast cancer.????

The optimal timing of Herceptin was evaluated in a Phase III clinical trial known as NCCTG N9831. The study enrolled women with Stage I-III HER2-positive breast cancer.? All women received chemotherapy with doxorubicin and cylophosphamide followed by paclitaxel, and some women also received Herceptin. Herceptin was started either at the same time as paclitaxel or later (after chemotherapy had been completed), and was given for a total of 52 weeks.????

Women who received both Herceptin and chemotherapy had a lower risk of cancer recurrence than women who received chemotherapy alone.?Women who started Herceptin at the same time as paclitaxel appeared to derive the most benefit. Five-year disease-free survival was 84.4% among women who received concurrent Herceptin and paclitaxel, compared with 80.1% among women who started Herceptin after finishing treatment with paclitaxel. This result did not meet the criteria for statistical significance, however, suggesting that it could have occurred by chance alone.?Starting Herceptin at the same time as paclitaxel did not appear to substantially increase the risk of side effects compared with starting Herceptin after chemotherapy had been completed.?

For women with early-stage, HER2-positive breast cancer, these results suggest that starting Herceptin during chemotherapy may produce better results than starting Herceptin after chemotherapy has been completed.?

Reference:?Perez EA, Suman VJ, Davidson NE et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. 2011;29:4491-4497.?

Posted December 4, 2011

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Adding Afinitor to Herceptin May Provide Breast Cancer Benefit

For women with HER2-positive breast cancer that worsens in spite of treatment with HerceptinR (trastuzumab), treatment with a combination of Herceptin and AfinitorR (everolimus) may provide a benefit. These results were published in the Journal of Clinical Oncology.????

Approximately 20-25% of breast cancers overexpress (make too much of) the HER2 protein. 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. One important focus of research is the treatment of cancer that has progressed after prior HER2-targeted therapy.???

Afinitor is an oral medication that works by inhibiting a protein known as mTOR. The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth.?Currently, Afinitor is used for the treatment of selected patients with kidney cancer, pancreatic neuroendocrine tumors, and subependymal giant cell astrocytoma (SEGA).?

To evaluate the combination of Herceptin and Afinitor, researchers combined information from two clinical trials that were conducted concurrently. Information was available for 47 women with HER2-positive metastatic breast cancer that had progressed during treatment with Herceptin. Study participants received Herceptin every three weeks in combination with daily Afinitor.????

Seven patients (15%) had a partial response to treatment (a reduction in detectable cancer).?An additional nine patients (19%) experienced stable disease for six months or longer. ?Median duration of survival without cancer progression was 4.1 months.?Side effects included fatigue, infection, and mouth sores (mucositis).?

These results suggest that the combination of Afinitor and Herceptin may benefit women with HER2-positive, advanced breast cancer that has worsened in spite of Herceptin treatment. Afinitor has been approved by the US Food and Drug Administration for other purposes, but has not yet been approved for breast cancer. At this time, the use of Afinitor would only be appropriate for women with ?HER2-positive breast cancer in the setting of a clinical trial.? Additional, ongoing studies are evaluating the combination of Herceptin, Afinitor, and chemotherapy in the first- and second-line treatment of metastatic breast cancer. ?

Reference: Khanh Morrow P, Wulf GM, Ensor J et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. Journal of Clinical Oncology. Early online publication July 5, 2011.?

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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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