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Ixabepilone plus capecitabine vs. capecitabine in metastatic breast cancer patients

Study Design:  Multinational randomized, open-label phase III trial
Study Eligibility:  Women with metastatic or locally advanced breast cancer who already had a prior chemotherapy regimen of anthracyline (i.e., doxorubicin or epirubicin) and taxane (i.e., paclitaxel or docetaxel)  
Enrollment: 1,221 patients
Research Question:  How does the combination of ixabepilone and capecitabine compare with capecitabine in terms of survival benefit in metastatic breast cancer patients?

In a previous phase III trial CA 163-046, patients treated with ixabepilone and capecitabine (Xeloda®) demonstrated significant improvement in progression-free survival (PFS) and objective response compared to patients treated with capecitabine alone. Patients in CA 163-046 were resistant to anthracyline therapy.

In this study, the investigators wanted to see if the combination of ixabepilone and capecitabine improved overall survival.  Women who were pretreated with anthracyline- and taxane-based chemotherapy regimens were randomized to either ixabepilone plus capecitabine or to capecitabine alone. The primary endpoint of the study was overall survival (OS). Secondary endpoints included PFS, objective response rate (ORR), time to response and response duration, safety, and patient-reported outcomes (PROs). 

At the time of the analysis, 430 deaths (71%) occurred among 609 patients treated with ixabepilone and capecitabine compared to 450 deaths (74%) among 612 patients treated with capecitabine alone. There was no significant difference in OS. PFS was significantly improved in patients receiving both ixabepilone and capecitabine compared to patients receiving capecitabine alone, confirming results from the previous trial. 

Treatment-related adverse events were primarily mild to moderate (grade 1 to 2) in patients receiving both drugs. The most frequent grade 3 to 4 nonhematologic adverse events were periphery sensory neuropathy, hand-foot syndrome, fatigue, diarrhea, myalgia, arthralgia, and stomatitis for combination group. The most frequent grade 3 to 4 adverse events in the capecitabine group were hand-foot syndrome, diarrhea, and stomatitis.

These results are similar to numerous trials that have demonstrated improved PFS and ORR with combination chemotherapy compared to single-agent chemotherapy. The toxicity profile of the ixabepilone and capecitabine combination did not differ significantly from capecitabine monotherapy.  But there was no difference in overall survival between the two treatment groups. Therefore, clinicians and patients will need to consider an appropriate risk-benefit ratio in choosing their optimal treatment regimen.