Health

Findings reported from early breast cancer deescalation therapy

The researchers said a complete pathological response was higher in a molecularly selected subgroup of patients with early-stage breast cancer treated with a combination of nonchemotherapy, including trastuzumab biosimilars.

In studies of early-stage breast cancer (EBC), including treatment with trastuzumab biosimilars (trasimilars), pertuzumab, and pembrolizumab, researchers found that molecular selection of a particular patient type was a complete pathological response (pCR). Observed to help improve.

In the findings of KEYRICHED-1 presented at the 2021 San Antonio Breast Cancer Symposium, researchers are more toxic when selecting patients with a subtype rich in human epidermal growth factor receptor 2 (HER2) by PAM50. He said he had a “clinically meaningful” pCR rate compared to chemotherapy. Regimen.

The trial was an effort to escalate breast cancer treatment that includes chemotherapy as standard. There is a desire to limit treatment options, as multiple drugs can result in overtreatment with unnecessary adverse events.

In this study, researchers enrolled patients with HER2-enriched (HER2-E) EBC, a PAM50 molecule subtype of HER2-positive breast cancer that tends to be associated with increased pCR rates after anti-HER2-based treatment. ..

Researchers have found newly diagnosed HER2-positive stages with immunohistochemical (IHC) expression (2+ or 3+) and HER2-E subtypes in the premenopausal and postmenopausal states (N = 48). Enrolled patients with EBC from I to III.

The regimen contained 4 cycles (every 21 days) of pembrolizumab 200 mg. Trastuzumab biosimilars, loading dose 8 mg / kg and maintenance dose 6 mg / kg; and pertuzumab, loading dose 840 mg / kg and maintenance dose 420 mg / kg.

Trastuzumab attaches to HER2-expressing cancer cells and blocks signaling that promotes their growth. Pertuzumab also blocks cell signaling and induces apoptosis or cell death. Pembrolizumab prevents cancer cells from shutting down the immune system through a programmed death route.

The study dates were May 2020 to March 2021, and researchers enrolled 52 patients with the HER2-E subtype (median age 57 years), 48 of whom started treatment. They stated that 65% had tumors larger than 2 cm and 30% were positive for lymph node metastases.

The centrally confirmed pCR rate was 52% in 46 evaluable patients. The researchers said pCR was observed in 20 (51.2%) of 39 patients with HER2-positive tumors with 3 + IHC expression.

The confirmed pCR rate for HER2-positive / hormone receptor (HR) -positive tumors was 38.5% compared to 58.5% for patients with HER2-positive / HR-negative tumors.

The survey results are WSG-ADAPT trial, Reported in 2017. This was a study of HER2-positive / HR-negative EBC patients. In this study, patients were randomized to trastuzumab and pertuzumab, or trastuzumab, pertuzumab, and paclitaxel.

The WSG-ADAPT trial did not select patients molecularly. In that study, researchers sought to assess the benefits of pCR with the addition of taxane therapy rather than deescalation therapy. In this case, taxane (paclitaxel) “substantially increased” the pCR of HER2-positive / HR-negative EBC patients over a 12-week study period.

“KEYRICHED-1 shows that by selecting the right molecular patient, we can achieve clinically meaningful pCR rates in the range available in regimens that include longer and more toxic chemotherapy,” he said. The authors of a recent trial concluded.

reference

Kuemmel S, Gluz O, Reinisch M, et al. KEYRICHED-1 – A prospective multicenter non-centered combination of pembrolizumab and trastuzumab and pertuzumab dual anti-HER2 blockers in patients with early-stage breast cancer with an endogenous subtype rich in molecular HER2-. Blinded neoadjuvant phase II single-arm study. Announcement location: 2021 SABCS; December 7-10, 2021. Poster P2-13-03.

ExBulletin

Findings reported from early breast cancer deescalation therapy