There is an increasing number of patients with metastatic breast cancer who are pretreated with taxanes in the (neo-) adjuvant situation. Therefore, it is essential to re-assess the efficacy of taxane-based treatment in this group of patients.
In this retrospective multicenter cohort study, we observed an overall response rate of 48.6%, consisting of 27.0% complete and 21.6% partial responses, with a median overall survival of 1.3 years in patients who received taxane-based treatment as first-line therapy. The response rate using taxane mono therapy was 40%, and using combination therapy, 54.5%. This is in the range of what was observed in trials including taxane-naive patients. 5 multicenter phase II trials for first-line treatment of metastatic breast cancer with docetaxel monotherapy of 75 or 100 mg/m2
reported an overall response rate between 38 and 68% and a median overall survival of 16.4 months across these studies [16
], and a phase III study assessing docetaxel and doxorubicin reported a response rate of 48% [17
]. Docetaxel in combination with doxorubicin, doxorubicin/cyclophosphamide, and trastuzumab reached response rates of 59, 61, and 77%, respectively [18
]. The response rate of paclitaxel monotherapy is largely dependent on dosing, infusion time and scheduling, and ranged between 22 and 62% [21
]. Combination of paclitaxel with doxorubicin as well as trastuzumab were highly effective, with response rates of 94 and 50%, but the former was associated with significant cardiotoxicity [23
The observed response rates with re-challenging a taxane appear higher than those with capecitabine, vinorelbine or ixabepilone in a similar setting, which were usually in the range of 20-30% [25
The strongest predictors for the effect of taxane re-challenge were the presence of visceral metastasis and the duration of the disease-free interval. The observed higher response rate in patients with a longer disease-free interval can be explained by the assumption that tumors with high resistance to taxanes recur earlier. However, the observed response rate of 34.8% in patients with a disease-free interval of < 1 year shows that the use of taxanes in this specific population also represents a valid option. Furthermore, as we received information of approximately 30% of the target population, a selection bias cannot be ruled out.
The response rate of tumor phenotypes according to hormone and HER2 receptor status was not significantly different; however, the rate was highest in HER2-positive tumors (being treated additionally with an anti-HER2 agent). Surprisingly, triple-negative tumors usually considered to be highly resistant to palliative chemotherapy showed a response rate as high as 50%. This is in line with data with anthracyclines and taxanes as neoadjuvant therapy, with a high pathologic complete response rate [26
The re-challenge of taxanes at a later line resulted in a much lower response rate; however, these patients were heavily pretreated. Due to the small number and the wide heterogeneity of this population, the only firm conclusion that can be drawn from this cohort study is that a third use of taxanes does not seem to result in a clinical benefit for the patient (even with a good response at first line) and should be avoided.
Re-challenging taxane as first- or later-line treatment for patients with recurrent disease after (neo-)adjuvant taxane-based chemotherapy appears to be a reasonable option, also for patients with triple-negative tumors.