Anthracycline chemotherapy shows no benefit in HER2-positive breast cancer
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Anthracyclines did not improve 3-year efficacy as part of a neoadjuvant chemotherapy regimen for patients with HER2-positive breast cancer, according to results of the TRAIN-2 study presented during the ASCO20 Virtual Scientific Program.
Anthracyclines also appeared associated with clinically relevant toxicity, long-term results of the phase 3 study showed.
A neoadjuvant anthracycline-free regimen of carboplatin, taxanes and dual HER2 blockade should be considered for all patients with stage II or stage III HER2-positive breast cancer, according to the researchers.
“Although anthracyclines are associated with increased cardiac toxicity and risk for secondary malignancies, they are still frequently used in the management of early HER2-positive breast cancer, especially in patients with a higher risk for recurrence,” Anna van der Voort, MD, researcher in the division of medical oncology at the Netherlands Cancer Institute, told Healio. “Previous research has shown similar efficacy with and without anthracyclines, but these studies used single HER2 blockade or had a noncomparative design.”
In the TRAIN-2 study, van der Voort and colleagues randomly assigned 438 patients with stage I to stage III HER2-positive breast cancer to treatment with 500 mg/m² 5-FU, 90 mg/m² epirubicin and 500 mg/m² cyclophosphamide followed by six cycles of 80 mg/m² paclitaxel on day 1 and 8 and carboplatin area under the curve (AUC) 6 (n = 219), or nine cycles of paclitaxel plus carboplatin alone (n = 219).
Both treatment regimens were combined with 6 mg/kg trastuzumab, with a loading dose of 8 mg/kg, plus 420 mg pertuzumab (Perjeta, Genentech), with a loading dose of 840 mg. All patients completed 1 year of trastuzumab, radiotherapy and endocrine therapy as indicated.
Results presented during the 2017 ASCO Annual Meeting and published simultaneously in The Lancet Oncology showed high pathological complete response rates after neoadjuvant chemotherapy with and without anthracyclines plus dual HER2 blockade (67% vs. 68%).
In the current study, van der Voort and colleagues reported 3-year EFS, OS and updated safety analyses.
Median follow-up was 49 months.
Results showed 23 EFS events occurred with anthracyclines compared with 21 EFS events without anthracyclines (HR = 0.9; 95% CI, 0.5-1.63).
Three-year EFS rates were 92.7% (95% CI, 88.3-96.2) with anthracyclines vs. 93.5% (95% CI, 90.4-96.6) without anthracyclines. Three-year OS rates were 97.7% (95% CI, 95.7-99.7) with anthracyclines vs. 98.2% (95% CI, 96.4-100) without anthracyclines
Three-year DFS rates were 94.1% (95% CI, 91.3-96.9) among patients who achieved a pathological complete response after neoadjuvant treatment vs. 85.1% (95% CI, 79.3-91.3) of patients who did not achieve pathological complete response (HR = 0.42; 95% CI, 0.23-0.78).
“We also found no evidence that higher-risk patients, such as those with lymph node metastases and/or stage III disease, require anthracyclines,” van der Voort told Healio. “Updated safety analyses confirmed that anthracycline use was associated with increased risk of febrile neutropenia, cardiac toxicity and chemotherapy-associated leukemia.”
Researchers noted that two patients in the anthracycline group developed acute leukemia.
“Further research should focus on de-escalating cytotoxic treatment in patients who achieve early and complete responses to neoadjuvant treatment, but also investigate the use of new agents in patients without complete responses,” van der Voort said. “The TRAIN-3 study is currently evaluating the efficacy of an image-guided de-escalation strategy that refers patients for early surgery in cases of early complete radiologic response during neoadjuvant treatment with carboplatin, paclitaxel, trastuzumab and pertuzumab. This study is expected to include 462 patients and is currently enrolling across 50 centers in the Netherlands.” – by Jennifer Southall
Reference:
van der Voort A, et al. Abstract 501. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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van der Voort A, et al. Abstract 501. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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