Preoperative THP & Postoperative HP in Patients who Achieve a Pathologic Complete Response

By Nadine M. Tung, MD

Dr. Tung (Beth Israel Deaconess Medical Center) is the study chair for this trial. The study co-chairs are Antonio Wolff, MD (Johns Hopkins University/The Sidney Kimmel Comprehensive Cancer Center), Angela DeMichele, MD, MSCE (University of Pennsylvania/Abramson Cancer Center), and Judy Tjoe, MD (Novant Health Forsyth Medical Center).

NCTN Group Study Champions: Ciara O’Sullivan, MB, BCh (Mayo Clinic) for Alliance, Sagar Sardesai, MD, MPH (The Ohio State University/Wexner Medical Center) for NRG Oncology, and Shou-Ching Tang, MD, PhD (University of Mississippi Medical Center) for SWOG.

EA1181/CompassHER2 pCR is a neoadjuvant trial for patients with clinical stage II or IIIa HER2-positive breast cancer. The study aims to determine if it is safe to omit adjuvant chemotherapy after surgery for patients with pathologic complete response (pCR) after 12 weeks of pre-operative THP (single-agent taxane plus trastuzumab and pertuzumab). EA1181 is a single-arm trial, and all patients in the study receive 4 cycles (12 weeks) of neoadjuvant THP (physician’s choice of weekly paclitaxel, nab-paclitaxel, or every 3-week docetaxel), then surgery.

If testing shows pCR at the time of surgery, patients will then complete a year of trastuzumab and pertuzumab (HP) plus hormonal therapy and radiation if indicated. If testing shows residual disease (RD), patients will receive standard post-operative adjuvant therapy and may enroll in other clinical trials, such as the companion study (A011801/CompassHER2 RD). The primary endpoint of CompassHER2 pCR is 3-year recurrence-free survival (RFS) for patients who have a pCR.

EA1181 opened in February of 2020 with an enrollment goal of 1250 participants. Accrual is strong despite the COVID-19 pandemic, and the trial consistently exceeds the original target of 35 new participants per month. Based on this success, the study team recently expanded the scope of the trial to explore a potential interaction between estrogen receptor (ER) status at baseline and survival outcome. The study’s enrollment goal is now 2156, and there are two primary endpoints: RFS in HER2-positive/ER-positive patients with pCR and RFS in HER2-positive/ER-negative patients with pCR. Thus, in addition to potentially changing clinical practice by maximizing treatment benefit and minimizing toxicity, CompassHER2 pCR may also uncover a relationship between ER status and patient outcomes.

Patients are eligible for CompassHER2 pCR if they have histologically confirmed HER2-positive primary invasive breast carcinoma, determined by local testing. Their hormone receptor (ER and PR) status must be known; patients with either hormone receptor-positive or hormone receptor-negative HER2-positive breast cancer are eligible. Additionally, participants’ cancer must be stage II or IIIa.

The CompassHER2 (COMprehensive use of Pathologic response ASSessment to escalate or de-escalate therapy in HER2-positive breast cancer) Trial Program is a collaboration between two NCI National Clinical Trials Network (NCTN) groups: ECOG-ACRIN Cancer Research Group and the Alliance for Clinical Trials in Oncology. Together, we investigate the optimization of therapy in patients with HER2-positive breast cancer. The trials within the CompassHER2 Program address clinical therapeutic objectives as well as translational questions. EA1181/CompassHER2 pCR was the first trial to open within the CompassHER2 Program. Alliance then opened CompassHER2-RD in July 2020.