Unlike in the adjuvant setting, there is no predetermined duration of treatment. Therefore, the duration of chemotherapy should be individualized taking into account the patient’s goals of treatment, presence of treatment toxicities, and alternative options that might be available. In general, patients should continue chemotherapy to the best response, disease progression, or if toxicity requires discontinuation of treatment.
For women who respond to chemotherapy, some data suggest that there are benefits to continuing treatment beyond their best response (ie, maintenance therapy):
- A 2011 meta-analysis of first-line treatment randomized trials that included almost 2300 women compared maintenance treatment with treatment over a prespecified duration (range, three to eight cycles) . Longer chemotherapy duration was associated with improvement in progression-free survival (PFS; hazard ratio [HR] 0.64, 95% CI 0.55-0.76) and overall survival (OS; HR 0.91, 95% CI 0.84-0.99).
- A randomized trial published in 2013 consisted of 324 patients with metastatic breast cancer, all of whom were treated with paclitaxel and gemcitabine . Patients who achieved disease control (complete or partial response, or stable disease) to treatment (n = 231) were randomly assigned to observation or maintenance chemotherapy with the same agents until disease progression.
The administration of maintenance chemotherapy resulted in a higher PFS rate at six months compared with observation (60 versus 36%, respectively; HR 0.73, 95% CI 0.55-0.97) and improved OS (median, 32 versus 24 months; HR 0.65, 95% CI 0.42-0.99). However, continuation of paclitaxel and gemcitabine resulted in a higher incidence of serious (grade 3/4) neutropenia (61 versus 0.9%) and grade 2/3 neuropathy (0.9 verus 0%).
Despite these findings, several issues limit the universal application of these data in metastatic breast cancer:
- Over 70% of patients in this study had hormone-positive breast cancer; of these patients, only about 20% of these women had received prior endocrine therapy and, for those in the control arm, endocrine therapy was not initiated after chemotherapy was discontinued.
- The median age of participants was 48, suggesting that younger patients were preferentially enrolled.
- The benefit in PFS was seen predominantly in the subgroup of women who were age <50 years, had hormone receptor-negative disease, had responded to chemotherapy, and had visceral disease.
While these data support maintenance chemotherapy for women with metastatic breast cancer, it should not be considered a universal approach to the treatment of these patients, especially when one considers the biologic heterogeneity of breast cancer and the multiple ways that disease can be treated. However, for the young patient who is responding to treatment, these data support the continuation of chemotherapy beyond best response, particularly if she accepts the increased risks of toxicity associated with continued chemotherapy .