Capecitabine for Metastatic ER+ Breast Cancer

Gretchen G. Kimmick, MD, MS:The other thing that I think about with choice of first-line therapy is the NCCN [National Comprehensive Cancer Network] guidelines. There have been issues lately because the NCCN guidelines recommend single agents because they’re less toxic. There is now literature that supports the use of single-agent therapy, sequentially, in metastatic disease, to maintain quality of life. And, they have been shown to be equally effective to starting with a multiagent regimen. The choice for a multiagent regimen would be made when you have a patient who is highly symptomatic. They initially have a bit higher response rate but have no proven benefit in survival, as long as patients have access to all of the agents in the multiagent regimen.

In this particular patient, capecitabine wouldn’t necessarily be thought of, according to the NCCN guidelines, as a standard first-line agent. But, she had an anthracycline and a taxane in the adjuvant setting, so it was acceptable. We also have some retrospective data in the literature that supports the fact that if you do start with capecitabine and look at survival over the long run, the survival isn’t any worse than if you start with a taxane. With her, with the lack of hair loss from capecitabine, the ability to take it as a pill, and the overall good tolerance in the metastatic setting, I think it was a great choice.

With regard to doublet or combination chemotherapy versus single-agent chemotherapy, there are some regimens that have been studied and have been shown to be very effective. Those would include docetaxel with capecitabine. I happen to like that regimen. When we get a good response to the combination, you can always stop one or the other. I usually stop the docetaxel and continue with single-agent capecitabine. I’ve had many patients do very well with that. There are other taxane combinations, like paclitaxel and gemcitabine, or gemcitabine and carboplatin. There are several of them. They’re all very effective but are more toxic than single agents.

Typically, if I’m starting a woman with hormone receptor-positive breast cancer on a chemotherapy agent because her cancer has become resistant to endocrine therapy, I’ll pick a single-agent option if she’s not highly symptomatic, like in this case. And then, I’ll use the single agents sequentially. My personal preference is to start with capecitabine, if the patient prefers an oral agent. Or, I will offer a weekly palliative chemotherapy regimen, like single-agent taxane, or single-agent eribulin, or gemcitabine, to get control of the disease without too many side effects so that he or she can go about their life and do what they would like to do.

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