Back Back
Therapy for High-Risk HER2+ EBC

CE / CME

Planning Therapy for High-Risk HER2-Positive Early-Stage Breast Cancer: Expert Viewpoint

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Nurses: 1.00 Nursing contact hour

Released: May 12, 2021

Expiration: May 11, 2022

Lee Schwartzberg
Lee Schwartzberg, MD
CME/CE Information

Activity

Progress
1
Course Completed

TRAIN-2: Study Design

The open-label, randomized, controlled phase III TRAIN trial evaluated the use of neoadjuvant chemotherapy with or without anthracyclines, with dual HER2+ blockade.26,27 Patients (N = 438) enrolled on this study had HER2+ EBC and were considered high risk, with stage II-III disease. Patients must have had a WHO performance score of 0/1 and a normal LVEF of ≥50%.

This study was a European trial and was designed differently than the US standard of care. Patients were randomized to receive either 3 cycles of anthracycline (5-fluorouracil/epirubicin/cyclophosphamide) plus trastuzumab/pertuzumab followed sequentially by 6 cycles of trastuzumab, pertuzumab, carboplatin, and docetaxel (TCHP) or the experimental arm of a nonanthracycline-based regimen that included 9 cycles of TCHP before surgery. Patients then continued adjuvant trastuzumab to complete 1 year of HER2-targeted therapy. The primary endpoint was the rate of pCR, and the secondary endpoints were safety, recurrence-free survival, breast cancer severity score, and OS. This study also looked carefully at cardiac endpoints.

Download
TRAIN-2: Primary Endpoint of pCR

In the TRAIN-2 study, both treatment groups achieved a high rate of pCR (67%-68%), and we now have additional information that supports the use of dual HER2-targeted therapy with neoadjuvant treatment.26,27 There was no difference in the rate of pCR between TCHP and 5-fluorouracil/epirubicin/cyclophosphamide plus trastuzumab and pertuzumab (68% vs 67%; P = .75).

This outcome was also consistent across the prespecified subgroups (tumor size, nodal positivity, hormone receptor status, and age). Therefore, one could make a strong argument that the large majority of patients do not require treatment with anthracyclines in the neoadjuvant setting.

Download
TRAIN-2: EFS and OS

The 3-year EFS and OS are essentially the same in both treatment arms of the TRAIN-2 study.27 In these higher-risk patient populations, the 3-year EFS is approximately 93% and the 3-year OS is approximately 98% with or without the use of anthracyclines.

Download
TRAIN-2: Safety at 3-Year Follow-up

When comparing the nonanthracycline and anthracycline regimens, the rates of grade ≥3 hematologic AEs were similar for neutropenia (54% vs 60%), anemia (21% vs 20%), and thrombocytopenia (19% vs 18%). There were some differences in the rates of febrile neutropenia, with 1% for the patients receiving a nonanthracycline regimen and 10% for those receiving an anthracycline regimen.

The rate of nonhematologic AEs also varied slightly. There was more grade ≥3 diarrhea with the nonanthracycline regimen than the anthracycline regimen (17% vs 12%, respectively), but the rates were relatively low considering patients received 9 cycles of therapy. There were similar rates of grade ≥3 peripheral sensory neuropathy (7% vs 5%), grade ≥3 fatigue (6% vs 4%), and grade ≥3 liver function abnormalities (4% vs 5%). There was more grade ≥3 hypokalemia in the anthracycline arm compared with the nonanthracycline arm (9% vs 4%, respectively).

There was a significant difference in cardiac toxicity when comparing the 2 treatment regimens. As anticipated, the patients receiving the anthracycline-containing regimen experienced 14% more LVEF declines than those in the nonanthracycline arm (P = .0016). There was also a significant worsening of the LVEF decline to <50% in 8% of patients in the anthracycline arm and 3% of patients in the nonanthracycline arm (P = .044).

LVEF was measured every 3 months for 1 year as is standard in clinical practice. Of importance, in this trial, the LVEF decline did not improve during normal follow-up in one third of the patients.

Download
BACK | NEXT