Which chemotherapy agents are used in the treatment of metastatic breast cancer?

Updated: Dec 27, 2019
  • Author: Pavani Chalasani, MD, MPH; Chief Editor: John V Kiluk, MD, FACS  more...
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Answer

In addition to taxanes and anthracyclines, a variety of other chemotherapeutic agents can be used as single agents or in combination with taxanes. Capecitabine (Xeloda) is an oral agent that essentially represents a sustained-release formulation of the older antimetabolite fluorouracil (5-FU) and provides the convenience of self-administration.

Drugs such as capecitabine have very little associated myelosuppression, and they are often chosen when the patient's bone marrow has been damaged by previous therapy or when there is a desire to coadminister a myelosuppressive agent for more rapid effect. As a single agent, capecitabine has an ORR of 25-30%, with minimal toxicity. When combined with a taxane, an ORR of 40-50% has been observed, along with a median overall survival benefit of 3-15 months.

Another antimetabolite, gemcitabine (Gemzar), is typically given in combination with paclitaxel, based on results from a phase III trial comparing paclitaxel with the combination regimen in locally advanced breast cancer (LABC) and metastatic breast cancer. A total of 529 patients were randomized to receive paclitaxel 175 mg/m2 on day 1 plus gemcitabine 1250 mg/m2 on days 1 and 8, or receive the same dose of paclitaxel alone every 3 weeks. ORR (41% vs 26%) and overall survival (18.6 mo vs 15.8 mo) were significantly higher with the paclitaxel/gemcitabine arm than with paclitaxel alone. [157]

Vinorelbine (Navelbine) is a vinca alkaloid that targets tubulin in the mitotic spindle and is administered intravenously, usually on a weekly basis. Vinorelbine is often used as a single agent following treatment with a taxane or anthracycline, yielding an ORR of 25%. However, when used as a first- or second-line agent, vinorelbine can have ORRs of up to 40%.

Palbociclib (Ibrance) is an inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 used for first-line treatment for ER-positive, HER2-negative metastatic breast cancer in postmenopausal women, in combination with the aromatase inhibitor letrozole. [158]  A phase II study in which progression-free survival (PFS) for women receiving palbociclib and letrozole was 20.2 months, versus 10.2 months for those on letrozole alone (P = 0.0004). [158, 159]

The CDK 4,6 inhibitor ribociclib (Kisqali) was approved by the FDA in March 2017 for postmenopausal HR+/HER- advanced or metastatic breast cancer in combination with letrozole. Approval was based on interim analysis results from the phase III MONALEESA-2 trial in postmenopausal women who had received no prior systemic therapy for their advanced breast cancer (n=668). Ribociclib plus letrozole yielded a PFS rate of 63% with a duration of 19.3 months, compared with a rate of 42.2% and a duration of 14.7 months with letrozole alone. [148]  

Since those data were published, a subsequent analysis with an additional 11 months of follow-up showed that the median PFS was 25.3 months with the ribociclib combination versus 16 months with letrozole alone, according to a company statement. [160]

As with hormone therapy, the likelihood of benefit from chemotherapy is related to the success achieved with the previous regimen. Although there are occasional gratifying responses to a drug used in the third- or fourth-line setting of metastatic breast cancer, they are the exception rather than the rule. Thus, patient characteristics, previous treatments, and the expected toxicity of these regimens must be taken into account.


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