A new study found little difference with regard to efficacy or toxicity between two chemotherapy regimens used in combination with trastuzumab in older women with HER2-positive breast cancer. One of the regimens, containing docetaxel, was associated with a higher likelihood of completing trastuzumab treatment.
Two adjuvant trastuzumab-based regimens have been widely used in the United States over the past 2 decades. A combination of doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) was approved first, in 2006, followed in 2008 by approval of docetaxel in combination with carboplatin and trastuzumab (TCH). “No head-to-head clinical trial has compared ACTH and TCH in terms of efficacy or toxicity, nor is one anticipated,” wrote study authors led by Katherine E. Reeder-Hayes, MD, MBA, of the University of North Carolina at Chapel Hill.
Because no prospective randomized data are likely to emerge, the researchers used the Surveillance, Epidemiology, and End Results (SEER) cancer registry and linked Medicare data to compare the two regimens. They included a total of 1,077 patients over the age of 65 years, 365 of whom received ACTH and 712 of whom received TCH; a propensity-matched subset of 416 patients received each regimen (208 each). Results of the study were published in the Journal of Clinical Oncology.
They found a substantial change in practice patterns over time. In 2005, 88% of patients received ACTH; by 2011, that proportion had dropped to 15%.
In terms of survival, there was no difference between the regimens. In the full cohort, the 5-year overall survival rate was 88% with ACTH and 93% with TCH, for a hazard ratio (HR) of 1.41 (95% CI, 0.94–2.11). In the matched subset of patients, the 5-year overall survival rate was 90% with ACTH and 92% with TCH, for an HR of 1.22 (95% CI, 0.63–2.35).
Breast cancer–specific survival did appear to be better with TCH, but only in the full cohort. At 5 years, the rate was 90% with ACTH and 96% with TCH, for an HR of 2.14 (95% CI, 1.29–3.53). In the propensity-matched patients, though, this difference was not significant, at 92% and 96%, respectively, for an HR of 2.08 (95% CI, 0.90–4.82).
There were some specific differences between the regimens with regard to toxicity. Neutropenia and anemia were more common with ACTH (P < .01), while dehydration was more frequent with TCH (P < .01). After propensity matching, the study found no significant differences with regard to the frequency of chemotherapy-related adverse events.
Healthcare use was also generally similar. Including emergency and observation visits, 34% of ACTH patients and 36.5% of TCH patients used hospital services within 6 months of beginning therapy (P = .46).
Among patients who received ACTH, 77% completed trastuzumab therapy, compared with 88% of TCH patients. Among the matched subset of patients, these rates were 77% for ACTH and 89% for TCH (P = .001).
“In the context of limited evidence in older patients, selection between these two regimens in older women on the basis of concerns for differential toxicity or efficacy may not be appropriate,” the authors concluded. “As adjuvant therapy for HER2-positive breast cancer evolves to include de-escalated chemotherapy and dual-targeted therapy, it is important to continue to evaluate real-world toxicity and effectiveness, supplementing and extending the contributions of prospective clinical trials.”