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

By Nadine M. Tung, MD

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.

Learn more about CompassHER2 pCR at ecog-acrin.org.

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 are 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.