TRAIN-2 trial leads to changes in HER2+ breast cancer treatment

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Neil Vasan, MD, PhD, assistant professor of medicine at the Herbert Irving Comprehensive Cancer Center, Columbia University, explains how the results of the TRAIN-2 trial (NCT01996267) have impacted the treatment of patients with breast cancer HER2-positive breast.

The Phase 3 TRAIN-2 trial randomized 438 patients with HER2-positive stage II or III breast cancer undergoing neoadjuvant therapy to receive 3 cycles of fluorouracil, epirubicin and cyclophosphamide followed by 6 cycles of paclitaxel and carboplatin, or 9 cycles of paclitaxel and carboplatin. Both groups received trastuzumab (Herceptin) and pertuzumab (Perjeta) every 3 weeks. The aim was to compare the event-free survival (EFS), overall survival (OS) and safety of a diet containing an anthracycline such as epirubicin versus a diet that did not.

At 3 years of follow-up reported in 2021, 10.5% of the anthracycline group had SES events versus 9.6% in the no-anthracycline group, with a relative risk of 0.90 in favor of the no-anthracycline group (CI to 95%, 0.50-1.63). Three-year EFS and OS were similar between groups: 92.7% and 97.7% in the anthracycline group versus 93.6% and 98.2% in the no-anthracycline group, respectively.

Based on the lack of benefit of anthracyclines and the risk of cardiotoxicity and other adverse events, regimens containing anthracyclines such as doxorubicin are no longer preferred in this setting. Now in favor are docetaxel, carboplatin, trastuzumab and pertuzumab.

TRANSCRIPTION:

0:08 | Another trial that has been very important from a treatment perspective is the Phase 3 TRAIN-2 trial. This trial addressed the question: are anthracyclines necessary in the treatment of [patients with] HER2-positive breast cancer, and patients received either chemotherapy with anti-HER2 treatment with a diet containing anthracyclines or a diet without anthracyclines.

The [EFS] the rates were similar, and there were a few caveats. For example, the way the anthracyclines were given every 3 weeks – generally, if they were given, we would give them every 2 weeks. But since no benefit was shown with the addition of an anthracycline, it changed the way oncologists treat HER2-positive breast cancers that might be a bit larger, a larger tumor, or patients with damage to the lymph nodes.

The predominant standard of care is a regimen called TCHP, which includes 2 chemotherapy drugs, docetaxel and carboplatin, along with trastuzumab and pertuzumab. Notably, it does not contain anthracycline, doxorubicin. This trial was so convenient to change that even [in] the NCCN [National Comprehensive Cancer Network] guidelines recently, the ACTHP [doxorubicin and cyclophosphamide followed by paclitaxel, trastuzumab, and pertuzumab] is not a preferred diet.

So I think that shows how much this has changed the therapeutic landscape for patients where we need to give therapy that is more standard and aggressive, but not too aggressive in order to be able to spare them from the AEs of anthracyclines, which include cardiotoxicity.

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