Benefit of Antibody Drug Conjugate T-DM1 in HER2+ BC

Sara M. Tolaney, MD, MPH:T-DM1 is an antibody drug conjugate that consists of trastuzumab linked to emtansine. Emtansine is a very potent antimicrotubule agent. When this antibody drug conjugate binds to HER2,it gets taken in intracellularly, and then the linker releases the emtansine intracellularly, resulting in cell death. So it’s a very clever mechanism to deliver very potent chemotherapy into the cancer cell. I think some people like to think of these antibody drug conjugates as smart bombs because of their very targeted delivery of chemotherapy.

Given data from KATHERINE, I do think that any patient who has residual disease after trastuzumab-based chemotherapy should be offered 14 cycles of TDM-1 because, again, it was associated with a 50% reduction in invasive disease-free survival events. I do think it also makes us realize the importance of giving therapy in the preoperative setting, because it allows us to better understand response to therapy and then tailor adjuvant treatment based on this response. Prior to KATHERINE people weren’t uniformly giving patients with locally advanced HER2-positive disease preoperative treatment. We knew data that suggested that preoperative therapy yielded similar outcomes to adjuvant therapy, and so we didn’t feel like we had to give the therapy in the preoperative setting. But now seeing that we can tailor treatment based on response to preoperative therapy, I think it should push us to utilize treatment preoperatively, particularly for those patients who have tumors larger than 2 cm, or who have clinically lymph node-positive disease.

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