Case Review: T-DM1 for Residual HER2+ Breast Cancer

Sara M. Tolaney, MD, MPH:This is a case of a 49-year-old woman who is postmenopausal and had palpated a mass in her right breast. She had seen her physician who had obtained a mammogram, which did demonstrate there was a 3-1/2 cm mass and this then prompted evaluation with biopsy, which confirmed that there was a high-grade invasive ductal carcinoma that was hormone receptor-negative. So estrogen receptor-negative, progesterone receptor-negative, and was HER2-positive and was 3-plus on immunohistochemical staining.

Given that she had an HER2-positive breast cancer, the decision had been made for her to get preoperative therapy and she had received docetaxel in combination with carboplatin and trastuzumab and pertuzumab for a total of 6 cycles. After that she had undergone breast surgery. She had elected to have a mastectomy and nodal evaluation, and she was found to have about a 1-1/2 cm of residual disease within the breast and no lymph node involvement. The decision at that point had been made for her to receive adjuvant therapy with T-DM1.

She had been on T-DM1 for about 3 cycles when she had started to develop some neuropathy, particularly within her hands. There were further discussions that then had to be made about how to proceed with treatment.

So generally I’ve been treating patients who have HER2-positive tumors that are greater than 2 cm or are clinically node-positive with preoperative treatment. When deciding what therapy to use, generally I am using a pertuzumab-based preoperative therapy since we know from, at least in the adjuvant setting, that pertuzumab seems to have its greatest benefit in those patients who either have node-positive disease or hormone receptor-negative disease. Since these are the patients who tend to benefit from pertuzumab, and since I’m using preoperative therapy in the higher-risk patient population, I am using a pertuzumab-based therapy.

So then then the question becomes which pertuzumab-based treatment to choose from. Now we do have data from NeoSphere that have looked at docetaxel in combination with trastuzumab and pertuzumab and had shown about a 40% pathologic complete response [PCR] rate, and so I think that [docetaxel/trastuzumab/pertuzumab] regimen is a reasonable choice. Alternatively, there is data from TRYPHAENA [clinical trial], which had looked at giving the TCHP regimen, so docetaxel, carboplatin, trastuzumab and pertuzumab, and demonstrated about a 60% pathologic complete response rate. And so generally I’m choosing between [docetaxel/carboplatin/trastuzumab/pertuzumab] or [docetaxel/trastuzumab/pertuzumab], although I will say…I think an alternative choice is to choose an anthracycline-based preoperative regimen. And so some people will use [doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab] as another treatment choice, but generally I am trying to pick a non-anthracycline-based treatment in the preoperative setting. I think in this particular patient’s case [docetaxel/carboplatin/trastuzumab/pertuzumab] was a very reasonable preoperative approach.

We know that preoperative pertuzumab-based therapy is highly effective, and about 40% of patients achieve a pathologic complete response with [docetaxel/trastuzumab/pertuzumab], and about 60% of patients achieve a pathologic complete response with [docetaxel/carboplatin/trastuzumab/pertuzumab]. We do however know that patients who have hormone receptor-negative, HER2-positive disease will achieve higher rates of pathologic complete response than those patients with hormone receptor-positive, HER2-positive tumors.

For example, in NeoSphere we saw a 26% pathologic complete response rate for hormone-receptor-positive, HER2-positive tumors compared with about a 63% pathologic complete response rate for hormone-receptor-negative, HER2-positive tumors. So having residual disease is more common in those patients with hormone-receptor-positive, HER2-positive tumors.

There are data to suggest that patients who have residual disease do have worse prognosis than patients who achieve pathologic complete response. So there was a very nice meta-analysis that had been done and published by Patricia Cortazar [MD] that had very cleanly demonstrated that particularly within the HER2-positive patients achieving a PCR was associated with better disease-free survival than those patients who failed to achieve a PCR.

We also have data from NeoSphere that showed that patients who achieve a pathologic complete response were disease-free at 5 years in 86% of patients compared with about 75% of patients who had residual disease. And this was also consistent with data from NeoALTTO showing very similar rates, again suggesting that patients who failed to achieve a PCR do have worse prognosis. So I do think that this piece of information is critical in better understanding how a patient’s long-term disease outcomes are going to be.

Transcript edited for clarity.

Case: A 49-Year-Old Woman With HER2+ Breast Cancer

H & P

• A 49-year-old woman was referred by gynecology for a mass in her right breast
• No children, menopause at age 45
• No history of cardiovascular disease, otherwise good health
• PE: revealed a woman of normal weight (BMI = 21 kg/m²), with a palpable mass in her right breast

Imaging

• Mammogram revealed 3.5-cm tumor in right breast
• CT: confirmed a tumor in right breast with no lymph node involvement

Biopsy and labs:

• Histology: ductal, grade 2
• ER(-), PR (-)
• HER2IHC: 3+
• BRCA1/2: negative

Treatment

• Diagnosed with ER/PR negativeHER2+ breast cancer; she received neoadjuvant TCH-P (docetaxel + carboplatin + trastuzumab + pertuzumab and achieved a partial response
  • Residual disease of 1.5 cm after neoadjuvant therapy
• Underwent mastectomy
• After discussing with her the options for adjuvant therapy, benefits and risks of each, and her goals, she was started on ado-trastuzumab emtansine (T-DM1)
• At present, she has completed 3 cycles of T-DM1
  • Reports numbness in her fingers, “like wearing gloves” that sometimes interferes with small tasks like buttoning a shirt