HMN 2025: How Pre-operative THP results in pCR in 64% of early-stage HER2+ ER- breast cancer sufferers

Patients with Stage II and III (early-stage) HER2+ breast cancer often endure preoperative remedy with multi-agent chemotherapy together with anti-HER2 antibodies, adopted by surgical procedure. A much less intensive, diminished chemotherapy remedy strategy is at the moment being evaluated within the CompassHER2 pCR trial by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN).

While longer follow-up is required to evaluate long-term outcomes, pathologic full response (pCR) charges and predictors of pCR are being shared on the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, detailing which sufferers could profit most from the brand new strategy.

“Neoadjuvant remedy with 12 weeks of THP led to a pCR charge of 64% in sufferers with early-stage HER2-positive, ER-negative breast cancer on the time of surgical procedure, in comparison with 33% for these with ER-positive tumors,” stated lead investigator Nadine M. Tung, MD, a medical oncologist at Beth Israel Deaconess Medical Center in Boston. “We additionally discovered that amongst ER-positive breast cancers, decrease degree of ER expression resulted in increased pCR charges.”

THP combines one chemotherapy drug (a taxane) with the HER2-targeting medication trastuzumab and pertuzumab. THP is a customary remedy for sufferers with metastatic HER2+ breast cancer. Previous small research have proven that sufferers with early-stage illness may also attain a pCR with much less intensive therapies like THP.

CompassHER2 pCR (EA1181) is the primary large-scale trial to guage this strategy and its final affect on survival. The routine being assessed on this single-arm, non-randomized trial is 12 weeks of preoperative THP (4 cycles of trastuzumab and pertuzumab (HP)) with weekly paclitaxel (12 weeks) or docetaxel (q3w x 4), adopted by surgical procedure.

Despite the COVID-19 pandemic, affected person enrollment within the trial was speedy, with 2175 contributors becoming a member of between February 2020 and October 2023. Among them, 2141 began THP. Disease development throughout THP occurred in solely 16 sufferers (0.7%).

“If sufferers achieved a pCR, they didn’t obtain any extra chemotherapy, solely HER2-directed antibodies after surgical procedure, in addition to radiation and endocrine remedy if indicated,” stated Dr. Tung. “Ultimately, this trial ought to set up if sufferers who haven’t any residual cancer at surgical procedure after THP can forgo additional chemotherapy.”

The major endpoint is 3-year recurrence-free survival, which requires longer follow-up.

The pCR charges introduced at ASCO (Abstract 501) are categorized by estrogen receptor (ER) standing and different traits. A subset of 569 sufferers underwent biopsies for evaluation utilizing the HER2DX pCR-score. This laboratory check assigns a low, medium, or excessive rating primarily based on tumor gene expression and scientific options.

It is already identified that amongst HER2+ breast cancer tumors, these which might be ER-negative have a better pCR charge in contrast to people who are ER-positive. This study reveals a number of different predictors of pCR in sufferers with Stage II and III HER2+ breast cancer. These embrace:

• ER-negative standing
• Lower ER expression (?70%) in ER+ tumors
• HER2 IHC of three+ (vs. IHC 2+/ISH+)
• Use of weekly paclitaxel fairly than every-3-week docetaxel
• Higher HER2DX pCR rating no matter ER standing

The evaluation didn’t discover an affiliation with the baseline scientific stage of illness.

While THP could cause a spread of unwanted effects, it’s much less poisonous than regimens that include a number of chemotherapy medication.

“The findings from this trial could in the end assist clinicians establish which sufferers with HER2+ breast cancer could possibly be spared from the toxicity of extra intensive chemotherapy,” stated Dr. Tung.

Provided by
ECOG-ACRIN Cancer Research Group