Optimizing the Management of TNBC With Eribulin

Reshma L. Mahtani, DO:I’ve really seen quite impressive responses with eribulin. I think that the therapy is highly efficacious and really useful in a patient population that is resistant to chemotherapy. The drug is approved after 2 lines of chemotherapy in the metastatic setting, and we do see diminishing returns when it comes to responses that we expect in patients who have had prior treatment. That being said, patients do respond to eribulin quite well and it is associated with a survival benefit. I have found the drug to be pretty well tolerated. Neuropathy does become an issue and is generally managed well. I don’t think that it has been an issue for me in terms of having to take anyone off a study based on neuropathy. Other issues include neutropenia, which can be handled with dose delays and dose reductions and the use of growth factor support.

If a patient is neutropenic, the package insert guidelines indicate that if they have an absolute neutrophil count of less than 1000/mm³on day 8, that dose should be delayed for up to a week. If there is no recovery after 2 weeks, that is an indication for dose reduction. There’s also the option of omitting the day 8 dose. I have in my practice been able to pretty regularly get patients on a schedule that they can tolerate. The first through second cycle is the time that we’re trying to identify the dose and schedule that are best tolerated by the patient.

Eribulin is associated with other adverse effects beyond the ones that we’ve already discussed, neutropenia and neuropathy being the major ones. There is some asthenia and fatigue. There can be issues with gastrointestinal side effects. But I think that’s pretty common with a lot of chemotherapy agents. The alopecia rate reported in the trial was about 45%, which is what I see in my practice. But I do find that as patients are treated with multiple lines of chemotherapy, the alopecia issue becomes less important to them, especially in the context of the survival benefit. I find that many patients don’t seem to have that as an issue, although of course, everyone is an individual and those discussions should be had on an individual basis.

In summary, I would say that we have the potential to have a lot of new therapies on the horizon for triple-negative breast cancer. It’s an exciting time for patients who have traditionally had a poor prognosis, and this is an area of high unmet need. I think many patients who have triple-negative breast cancer and have larger tumors or lymph node involvement are increasingly being treated in the neoadjuvant setting. We have studies that are looking at what to do with patients who have residual disease and don’t achieve a pathologic complete response, as we know those patients are at higher risk for recurrence.

There are many drugs that are on the horizon for triple-negative breast cancer patients, including checkpoint inhibitors and vaccine studies in the adjuvant setting. For patients who harbor aBRCAmutation, the PARP inhibitor olaparib is now an exciting new therapy for patients. In terms of eribulin in the treatment of metastatic triple-negative breast cancer, I do think that this is a highly efficacious and well-tolerated treatment with a survival benefit, which is a hard thing to achieve as demonstrated by multiple other studies that have not been able to identify a survival benefit. The treatment is very well tolerated and highly efficacious.

Transcript edited for clarity.

A 55-year-old Woman With Advanced TNBC

June 2015

• Patient History
  • A postmenopausal 55-year-old African American woman who was first diagnosed with breast cancer 2 years ago after discovering a lump in her right breast
  • SH: active with 2 teenaged children
  • Imaging revealed the likelihood of a multifocal lesion (2.5 cm.) in the right breast and right axillary lymph node involvement
• Pathology findings from ultrasound-guided core needle biopsy:
  • Histologic grade 3 invasive ductal carcinoma
  • Hormone receptor status: ER(-), PR(-)
  • HER2(-) IHC, 0
• BRCA1/2testing, negative
• She underwent mastectomy followed by immediate reconstruction; 2 of 20 nodes positive
  • Surgical staging T2pN1M0
• Following surgery, she received adjuvant doxorubicin/cyclophosphamide followed by paclitaxel (12 weeks); pt. had difficulty completing CT due to significant diarrhea and CINV

October 2017

• Routine follow up at 18 months:
  • Patient reported having worsening cough and abdominal pain
  • Imaging revealed 3 lesions in her right lung (<2 cm) and several liver lesions
  • Biopsy confirmed metastatic TNBC
• She was started on treatment with gemcitabine/carboplatin; she required dose reduction for neutropenia; imaging at 3 months showed stable disease

May 2018

• Seven months after starting gemcitabine/carboplatin, imaging showed progression in a single right lung nodule (now 3.2 cm)
• After discussion of her therapy choices, the patient opted for treatment with capecitabine

August 2018

• Imaging at 3 months showed 4 new liver lesions
• She started treatment with eribulin 1.4 mg/m²IV on days 1 and 8 of each 21-day cycle
  • Two weeks after her first dose, she developed grade 3 neutropenia without fever