The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Long-term follow-up of a phase 3 study showed that anthracycline-based neoadjuvant chemotherapy did not improve event-free survival (EFS) or overall survival (OS) in patients with HER2-positive, nonmetastatic breast cancer compared with a taxane-platinum regimen when trastuzumab and pertuzumab were coadministered with chemotherapy. These findings were presented during the ASCO20 Virtual Scientific Program.1

Although anthracyclines have known activity in HER2-positive breast cancer, concerns related to the cardiotoxicity of regimens including both an anthracycline and trastuzumab have limited their use in this setting. More recent evidence supporting the safety of epirubicin plus trastuzumab combination therapy, however, led to the design of a phase 3 clinical trial in which neoadjuvant chemotherapy with an epirubicin-based regimen was compared with a non-anthracycline-containing regimen, both administered in combination with trastuzumab and pertuzumab, in the setting of HER2-positive breast cancer.

In this randomized, multicenter, open-label phase 3 trial (TRAIN-2; Identifier: NCT01996267), patients with stage II/III HER2-positive breast cancer were randomly assigned in a 1:1 ratio to receive neoadjuvant chemotherapy with either 3 cycles of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) followed by 6 cycles of paclitaxel plus carboplatin (219 patients) or 9 cycles of paclitaxel plus chemotherapy (219 patients). HER2-targeted therapy with both trastuzumab and pertuzumab were coadministered with chemotherapy, with patients completing 1 year of adjuvant trastuzumab with radiotherapy and adjuvant endocrine therapy as indicated.

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At a median follow-up of 19 months, a previously published analysis of results from 418 patients in this trial showed no difference in the primary study end point of pathologic complete response (pCR) rate when patients treated with an anthracycline (67%) and without an anthracycline (68%) were compared (P =.95).In addition, a significantly higher rate of at least grade 3 febrile neutropenia were observed in the anthracycline-containing arm (10%) compared with the anthracycline-free arm (1%; P =.0001).2

In this analysis, undertaken at a median follow-up of 49 months, 3-year EFS rates were 92.7% and 93.5% for those treated with and without an anthracycline, respectively (hazard ratio [HR], 0.90; 95% CI, 0.50-1.63; non-significant difference in favor of non-anthracycline regimen). No significant differences in 3-year EFS were observed in patient subgroups defined according to patient age, hormone-receptor status, tumor size, nodal status, or disease stage/grade.

Rates of 3-year OS were 97.7% for those receiving anthracycline-based chemotherapy compared with 98.2% for those treated with a chemotherapy regimen containing only paclitaxel and carboplatin (HR, 0.91; 95% CI, 0.35-2.36).

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Overall, disease-free survival was significantly improved in those who achieved a pCR (94.1%) compared with those who did not (85.1%; HR, 0.42; 95% CI, 0.23-0.78).

No new safety signals were observed in this analysis, although the frequency of patients with reductions in left ventricular ejection fraction defined as at least 10% from baseline and less than 50% was significantly higher for those receiving epirubicin versus not (8% vs 3%; P =.044), with no return of cardiac function in approximately one-third of patients. Two patients in the epirubicin-containing arm developed chemotherapy-associated acute leukemia.

In their concluding comments, the study authors noted that “a neoadjuvant carboplatin-taxane based regimen with dual HER2-blockade can be considered in all stage II-III breast cancer patients, regardless of hormone receptor and nodal status.”

Disclosure: Research funding for this study was provided by Roche. Please refer to reference for a complete list of disclosures.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.


  1. Van der Voort A, van Ramshorst MS, van Werkhoven ED, et al. Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 501.
  2. van Ramshorst MS, van der Voort A, van Werkhoven ED, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): A multicentre, open-label, randomised, phase 3 trial.  Lancet Oncol. 2018;19:1630-1640.