Breast
Fatima Cardoso, n/a
Champalimaud Clinical Centre
Champalimaud Foundation, Lisbon, Portugal, United States
Joyce O’ Shaughnessy, MD
Celebrating Women Chair in Breast Cancer Research
Baylor University Medical CenterTexas Oncology, US Oncology Network, Dallas, TX, USA, United States
Heather McArthur, MD MPH (she/her/hers)
University of Texas Southwestern Medical Center
Dallas, TX, USA
Dallas, Texas, United States
Heather McArthur, MD MPH (she/her/hers)
University of Texas Southwestern Medical Center
Dallas, TX, USA
Dallas, Texas, United States
Heather McArthur, MD MPH (she/her/hers)
University of Texas Southwestern Medical Center
Dallas, TX, USA
Dallas, Texas, United States
.jpg "Peter Schmid, n/a photo")
Peter Schmid, n/a
Centre for Experimental Cancer Medicine
Barts Cancer Institute, Queen Mary University London, London, UK
London, United States
Javier Cortes, n/a
International Breast Cancer Center
Quironsalud Group, Barcelona, Spain and Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain, United States
Nadia Harbeck, n/a
Breast Center, Dept. OB&GYN
LMU University Hospital, Munich, Germany, United States
Melinda L. Telli, n/a
Stanford University School of Medicine
Stanford, CA, USA, United States
David W. Cescon, n/a
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, United States
Peter A. Fasching, n/a
University Hospital Erlangen
Comprehensive Cancer Center Erlangen-EMN, Bavarian Cancer Research Center (BZKF), Erlangen, Germany, United States
Zhimin Shao, n/a
Department of Breast Surgery
Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China, United States
Delphine Loirat, n/a
Institut Curie
Paris, France, United States
Yeon Hee Park, n/a
Samsung Medical Center
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, United States
Manuel Gonzalez Fernandez, n/a
Hemato Oncólogo
IMAT-Oncomedica, Montería, Colombia, United States
Gábor Rubovszky, n/a
National Institute of Oncology
Budapest, Hungary, United States
Seock-Ah Im, n/a
Seoul National University Hospital
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea, United States
Rina Hui, n/a
Westmead Breast Cancer Institute
Westmead Hospital and the University of Sydney, Sydney, NSW, Australia; Centre of Cancer Medicine, the University of Hong Kong, Hong Kong, United States
Toshimi Takano, n/a
The Cancer Institute Hospital of JFCR
Tokyo, Japan, United States
Fabrice André, n/a
Faculté de Medicine Paris-Sud XI
Gustave Roussy, Villejuif, France, United States
Hiroyuki Yasojima, n/a
Department of Surgery Breast Oncology
NHO Osaka National Hospital, Osaka, Japan, United States
Zhenzhen Liu, n/a
Department of Breast Disease
Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China, United States
Pts with T1c-2 (≥2 cm) cN1-2 or T3-4 cN0-2, centrally confirmed, grade 3, invasive ductal ER+/HER2− breast cancer were randomized 1:1 to receive neoadjuvant pembro 200 mg Q3W or pbo, both given with paclitaxel QW for 12 wk, then 4 cycles of doxorubicin or epirubicin + cyclophosphamide (neoadjuvant treatment). After definitive surgery (± radiation therapy), pts received pembro or pbo for 9 cycles + standard ET. Stratification factors include region, tumor PD-L1 status, nodal involvement, ER positivity, and anthracycline schedule. Dual primary endpoints are pCR (ypT0/Tis ypN0) and EFS. Secondary endpoints include OS, pCR defined as ypT0 ypN0 and ypT0/Tis, and safety. RCB was an exploratory endpoint and was assessed by a local pathologist at the time of surgery. RCB-0, -1, -2, and -3 denote increasingly larger residual disease.
Results:
1278 pts were randomized to pembro + chemo (n=635) or pbo + chemo (n=643). At the final pCR analysis (May 25, 2023, first interim analysis data cutoff), median follow-up was 33.2 mo (range, 9.7-51.8). In the ITT population, pembro + chemo showed a statistically significant improvement in pCR (ypT0/Tis ypN0) vs pbo + chemo: 24.3% (95% CI, 21.0-27.8) vs 15.6% (95% CI, 12.8-18.6); estimated difference, 8.5 percentage points (95% CI, 4.2-12.8); P=0.00005; results were consistent for the secondary pCR definitions, ypT0 ypN0 (21.3% vs 12.8%) and ypT0/Tis (29.4% vs 18.2%). The benefit of pembro + chemo on pCR was generally consistent in the prespecified subgroups. There were more pts with RCB-0 (24.7% vs. 15.6%) and RCB-1 (10.2% vs 8.1%) and fewer pts in the RCB-2 (40.8% vs. 45.3%) and RCB-3 categories (20.5% vs. 28.9%) in the pembro group versus the pbo group. In the neoadjuvant phase, grade ≥3 treatment-related AE rates were 52.5% with pembro + chemo and 46.4% with pbo + chemo, with 1 death in the pembro arm due to acute myocardial infarction. EFS results are immature and continue to be evaluated.
Conclusions:
Addition of pembro to chemo significantly increased the pCR rate and shifted RCB to lower residual disease categories in pts with early-stage high-risk ER+/HER2− breast cancer. Safety was consistent with the known profiles of each regimen.