Early-stage HER2-Positive Breast Cancer Benefits from Neoadjuvant Chemotherapy

A new chemotherapy regimen demonstrated significant clinical activity in patients with HER2-positive, early-stage breast cancer, according to long-term follow-up data.

Hans-Christian Kolberg, MD

Neoadjuvant chemotherapy with docetaxel (Taxotere), carboplatin, and weekly trastuzumab (Herceptin)—the TCH regimen—demonstrated significant clinical activity in patients with HER2-positive, early-stage breast cancer, according to long-term follow-up data presented at the 2015 Breast Cancer Symposium.

A total of 51 patients were treated with the chemotherapy regimen of docetaxel at 75 mg/m2, carboplatin (AUC 6) 3 times weekly, and trastuzumab at a 4-mg/kg—loading dose followed by 2 mg/kg once weekly. At a median follow-up of 4.5 years, the overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS) rates were 94.18%, 82.35%, and 90.2%, respectively. Of the 21 patients who experienced a pathologic complete response (pCR), the OS rate was 100%.

The mean age of diagnosis was 55 years, 68.6% had ER-positive tumors, 39.2% presented with grade 3 disease, and 49% were node positive. Patients were monitored by ultrasound and then underwent surgery following 6 cycles of the TCH regimen. Trastuzumab was still administered to these patients 3 times weekly up to 1 year after surgery.

Earlier studies examined the effects of neoadjuvant treatment with TCH and how it is as effective as anthracycline-containing regimens, though survival data had not yet been published, explained lead study author Hans-Christian Kolberg, MD, doctor of Medicine, Marien Hospital Bottrop in Bottrop, Germany. The median follow-up results, he added, are commensurate with results from the HERA and BCIRG 006 studies, which looked at the efficacy of trastuzumab in the adjuvant setting.

“After we learned about the results of the BCIRG 006 study, which compared an anthracycline-containing regimen with docetaxel, carboplatin, and trastuzumab in the adjuvant setting, we were interested to see if that works in the neoadjuvant setting, too,” said Kolberg.

“This is because we believe that the sooner the tumor gets the antibody, it is better for the patient. We did not want to wait for surgery, but the other paradigm is that, we are treating any patient we know will need chemotherapy in a neoadjuvant fashion. Only in situations where we did not know the patients had cancer, or there were unexpected findings of the postoperative histology, they would receive adjuvant therapy.”

According to Kolberg, neoadjuvant therapy is not only an academically interesting idea to test chemotherapies and the effective therapies, but it is also simply doing the same thing before surgery as what you are doing in the adjuvant setting. He added that it opens a diagnostic and prognostic window for the patient.

“If she has a pCR, we can talk about her prognosis, which is a lot more information than we have if we just apply adjuvant chemotherapy and just wait to see if she responds or not. That is why we treated patients in the neoadjuvant setting,” he said.

“We decided to do a follow-up, and we identified 51 patients where we had a full follow-up. The outcome data that we found compared favorably to the known outcome data for adjuvant trials with trastuzumab. The patient group we have been treating is a classical neoadjuvant group with several grade 3 patients. Fifty percent of the patients were node-positive, and of course, all of them were HER2-positive, and 60% to 68% were ER-positive."

For the study, tumors were marked with titanium clips and before patients received 6 cycles of docetaxel and carboplatin with trastuzumab. After the 6 cycles, surgery was performed and in the cases of involved lymph nodes, the axillary dissection took place after the neoadjuvant chemotherapy.

According to Kolberg, a pCR rate of around 50% was found and, in 26 patients who had involved lymph nodes, 71% of these patients conversed to nodal-negative after therapy. He added that looking at the outcome data, patients who achieved a pCR had an OS rate of 100% after 54 months.

“What was a little stunning was that the ER-positive patients did extremely well, which was not expected. We would have expected these patients to maybe need an anthracycline or a longer therapy, perhaps eight cycles instead of six cycles,” said Kolberg.

Kolberg said that he envisions this treatment as being a major part of the way HER2 is treated in the future, considering the OS was “around 98%."

“I believe that it will consist of the combinations of taxanes and carboplatin with HER2-directed therapy, whatever that may be. It is possible to apply this therapy and start with trastuzumab immediately. Approximately 2 or 3 years ago, we learned that it is possible to give anthracyclines and trastuzumab at the same time, but this is something rather new,” he said.

Kolberg HC, Akpolat-Basci L, Stephanou M, et al. Neoadjuvant chemotherapy with docetaxel, carboplatin, and weekly trastuzumab (TCH) activity in HER2-positive early breast cancer: results after a median follow-up of 4.5 years.J Clin Oncol. 2015;33 (suppl 28s; abstr 140).