The DECRESCENDO trial

In this video, Dr Elisa Agostinetto comments on the poster she presented at SABCS 2024: De-escalation of chemotherapy in patients with HER2positive, hormone receptor-negative, node-negative early breast cancer: primary results of the phase II DECRESCENDO trial 

The DECRESCENDO trial is a phase II, investigator-initiated study designed to evaluate whether chemotherapy can be safely de-escalated in patients with HER2+ early breast cancer. This approach is rooted in the understanding that HER2+ breast cancer patients generally achieve excellent outcomes when treated with anti-HER2 therapies but that the use of chemotherapy, particularly anthracyclines, carries a risk of long-term adverse effects. The trial seeks to determine whether a specific group of patients can avoid anthracycline-based regimens without compromising treatment efficacy.

The study included patients with HER2+/ HR-, node-negative early breast cancer, and tumour sizes between 15 and 50 millimetres. In the neoadjuvant setting, participants were treated with weekly paclitaxel combined with a fixed-dose subcutaneous combination of trastuzumab and pertuzumab for 12 weeks. After surgery, adjuvant therapy was tailored based on the pathological response. Patients who achieved a pCR continued treatment with trastuzumab and pertuzumab for up to a year. For those with residual disease, treatment was escalated to include T-DM1, and in cases with significant residual disease (RCB 2 or greater), adjuvant anthracycline-containing chemotherapy was added before T-DM1. To assess the biological underpinnings of treatment responses, baseline tissue biopsies were analysed using PAM50 molecular subtyping, performed centrally at the Institut Curie. This allowed for a closer examination of the relationship between molecular subtypes and treatment efficacy.

The interim results presented included data from 139 enrolled patients, with 131 undergoing surgery. The overall pCR rate was 86%, indicating a strong response to the treatment regimen. Patients with the HER2-enriched PAM50 molecular subtype showed even higher pCR rates at 89%. Notably, some patients with the basal-like PAM50 subtype, which typically responds poorly to anti-HER2 therapy, also achieved pCR, highlighting the potential for variability in responses within this subgroup. Although survival outcomes, including relapse-free survival, were not yet mature enough for presentation, the trial’s initial findings suggest that an anthracycline-free regimen is associated with high efficacy in this carefully selected population. The results underscore the possibility of reducing treatment toxicity while maintaining excellent outcomes. Further follow-up is needed to assess the durability of responses and long-term survival benefits. Future analyses will help determine whether this de-escalated approach could redefine the standard of care for a subset of HER2+ breast cancer patients.