Comparison of Doxorubicin and Cyclophosphamide Versus Single-Agent Paclitaxel As Adjuvant Therapy for Breast Cancer in Women With 0 to 3 Positive Axillary Nodes: CALGB 40101 (Alliance)

Abstract

Purpose Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity. Patients and Methods Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported. Results With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T. Conclusion This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.

Patients with Slowly Proliferative Early Breast Cancer Have Low Five-Year Recurrence Rates in a Phase III Adjuvant Trial of Capecitabine

“…The tolerability of XT was better in NSABP-B40 when these agents were administered before AC (21). Even with 70% of the patients having node-positive disease, the number of DFS events was much lower than expected, as has been observed in a number of adjuvant breast cancer trials (27)(28)(29)(30). This low event rate substantially decreased the power of the study to show superiority of the AC!XT arm.…”

Clinical Validation of PITX2 DNA Methylation to Predict Outcome in High-Risk Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy

“…Also taxanes have significant toxic side effects, especially polyneuropathy. It has been shown that anthracycline-free regimens are not inferior to anthracyclines [3]. The question arises whether patients require both chemotherapy components and whether some patients might be sufficiently treated with anthracycline or taxanes alone.…”

Controversial issues in the management of older adults with early breast cancer

“…Despite the single-agent paclitaxel failing to show non-inferiority to AC, favorable toxicity profile and only 1% OS absolute difference made paclitaxel a reasonable option for unfit patients needing chemotherapy [59].…”