Eribulin in Recurrent Metastatic ER+ Breast Cancer

Gretchen G. Kimmick, MD, MS:In 2018, when her cancer had progressed on capecitabine, we’d gotten a partial response from capecitabine and were thinking about other options. We chose eribulin because there’s randomized trial data from the EMBRACE trial that suggests that it makes overall survival better versus another agent, based on the physician’s choice. That trial studied standard-dose eribulin versus a treatment of physician’s choice, like vinorelbine, gemcitabine, or one of the other regimens, or even capecitabine.

The overall survival was better in that trial, which was great. The time to progression was better, and the tolerance of the drug was very good. So, that was a good choice at that point. Other choices would be to switch to combination chemotherapy, which I wouldn’t necessarily favor because of the reasons I stated just a little while ago—the doublet and triplet combinations are more toxic than single-agent therapy.

So, I would pick a single agent next. Eribulin is a great choice because of the overall survival benefit. Vinorelbine, gemcitabine, and other single agents that are approved for breast cancer would also have been reasonable choices for her, as long as you’re paying attention.

My general rule, when I’m treating metastatic disease, is that if the cancer responded to one treatment, it has a good likelihood of responding to the next treatment. There are certain numbers of regimens that are available. I try them sequentially until it’s obvious that the patient has a cancer that’s become resistant to most chemotherapies. When I have a patient who has had cancer, who has progressed through one endocrine therapy and goes on chemotherapy and doesn’t respond to the first one—you see disease progression when you check scans for the first time—the chances that they’ll respond to the next one are pretty low.

I usually try to pick something with a different mechanism. If they don’t respond to that one after the first 3 months of scans, that’s a really poor prognostic factor. Then, we start talking about clinical trials, which we talk about all along. We also consider the option of hospice. Some studies have now shown that hospice and really aggressive palliative care can keep the body in good shape and can keep people around longer than if they are given cytotoxic therapy, which is toxic to the body and doesn’t control the cancer.

The toxicities most commonly seen with eribulin are low blood counts (cytopenia) and neuropathy. There are some other rare side effects like fatigue. I haven’t seen very many people get stomatitis, but that can happen.

When someone gets low blood counts from eribulin, the practice is to decrease the dose. You wait until the patient’s blood counts recover so that their neutrophil count is less than grade 1 and they’re safe to get another dose. You then decrease the dose to the next lower dose level—1.1 mg/m²from 1.4 mg/m²—for 2 weeks in a row. Then, you monitor blood counts at every single dose of eribulin so that you make sure that they’re safe getting the dose.

The same is true for any other grade 3 or 4 toxicity that is experienced during treatment. The common toxicity criteria are used. If they have mouth sores, grade 3, and they’re not eating well, the treatment gets reduced. We also dose reduce for hepatic dysfunction and renal dysfunction.

Transcript edited for clarity.

A 52-Year-Old Woman with MetastaticER+ Breast Cancer

March 2015

• A 52-year-old postmenopausal woman was referred for multidisciplinary assessment after being diagnosed with breast cancer, found incidentally on routine screening mammogram
  • Breast MRI revealed a 55-mm lesion in her left breast
  • FH includes a great aunt on her mother’s side who died of breast cancer at age 50
  • gBRCA1/2negative
• She underwent lumpectomy with axillary staging
• Biopsy findings:
  • Histology: invasive ductal carcinoma, grade 3
  • Hormone receptor status: ER+/ PR (-)
  • HER2,IHC 1+
  • OncotypeDx RS-high (27)
• Staging, T3BN0M0
• ECOG 1
• She completed 4 cycles of dose-dense doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel; she was then started on adjuvant letrozole

April 2017

• On routine follow-up, chest CT with contrast showed 4 small nodules in the left lung; biopsy confirmed metastatic breast cancer
  • Letrozole was changed to fulvestrant; imaging at 3 months showed progressive disease
  • She was subsequently started on treatment with capecitabine; imaging at 3 and 6 months showed a partial response
  • She was scanned for pulmonary embolism

April 2018

• On routine follow-up:
  • The patient complained of fatigue and new onset chest pain with deep breathing
  • FDG PET/CT showed 2 new liver lesions and progression in the lung lesions
  • ECOG 1
  • The patient was started on eribulin IV, with a dosing schedule of days 1 and 8, every 21 days