2019 ASCO Annual Meeting!
Session: Breast Cancer—Metastatic
Type: Oral Abstract Session
Time: Tuesday June 4, 9:45 AM to 12:45 PM
Location: Hall D1
SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx).
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 1000)
Author(s): Hope S. Rugo, Seock-Ah Im, Gail Lynn Shaw Wright, Santiago Escriva-de-Romani, Michelino DeLaurentiis, Javier Cortes, Shakeela Wazeen Bahadur, Barbara B. Haley, Raul H. Oyola, David A. Riseberg, Antonino Musolino, Fatima Cardoso, Giuseppe Curigliano, Peter A. Kaufman, Mark D. Pegram, Sutton Edlich, Sam Hong, Edwin P. Rock, William John Gradishar; University of California San Francisco Comprehensive Cancer Center, San Francisco, CA; Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea; Florida Cancer Specialists & Research Institute, New Port Richey, FL; Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Medical Oncology Service, Barcelona, Spain; National Cancer Institute “Fondazione Pascale,” Department of Breast and Thoracic Oncology, Naples, Italy; IOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Bannerer MD Anderson Cancer Center, Breast Cancer Program, Gilbert, AZ; University of Texas Southwestern Medical Center, Internal Medicine, Dallas, TX; Northwest Georgia Oncology Centers, Marietta Cancer Center, Marietta, GA; Mercy Medical Center, Division of Medical Oncology and Hematology, Baltimore, MD; University Hospital of Parma, Medical Oncology and Breast Unit, Parma, Italy; Champalimaud Clinical Center/Champalimaud Foundation, Breast Unit, Lisbon, Portugal; University of Milano, European Institute of Oncology, Division of Early Drug Development, Milan, Italy; University of Vermont Cancer Center, Breast Oncology, Division of Hematology/Oncology, Burlington, VT; Stanford Women’s Cancer Center, Breast Cancer Oncology Program, Palo Alto, CA; MacroGenics, Inc., Rockville, MD; Northwestern University, Division of Hematology/Oncology, Chicago, IL
Background: Pretreated HER2+ MBC lacks a defined standard of care, although T is commonly used. M has similar HER2 binding and antiproliferative effects as T. By contrast, M’s Fc region is engineered to increase affinity for both alleles of the activating Fc receptor (FcR), CD16A, and decrease affinity for the inhibitory FcR, CD32B. The low affinity CD16A-158F allele (~85% of population) has been associated with diminished clinical response to T. In a Phase 1 trial, M demonstrated acceptable safety, anti-tumor activity, and evidence of HER2-specific antibody and T-cell responses. Methods: SOPHIA (NCT02492711), a randomized, open-label P3 trial, enrolled pts with HER2+ MBC after pertuzumab and 1–3 lines of prior Tx for MBC. Pts were randomized 1:1 to M (15 mg/kg IV q3w + C) or T (6 [8 for loading dose] mg/kg IV q3w + C), stratified by met sites (≤2, > 2), lines of Tx for met disease (≤2, > 2), and C choice (standard dose capecitabine, eribulin, gemcitabine, or vinorelbine). Primary endpoints are central blinded PFS and OS, assessed sequentially using the stratified log-rank test. Objective response rate (ORR) was a secondary endpoint. 257 PFS events were required to provide 90% power to show PFS superiority at 2-sided α = 0.05. Results: Intent-to-treat analysis (536 pts: M 266; T 270) occurred after 265 PFS events. M prolonged PFS over T (median 5.8 vs 4.9 mo, hazard ratio [HR], 0.76; 95% CI, 0.59–0.98; P= 0.033). Treatment effects were more pronounced in pts with CD16A genotypes containing a 158F allele (median PFS 6.9 vs 5.1 mo, HR, 0.68; 95% CI, 0.52–0.90; P= 0.005). In 524 pts with baseline measurable disease (M 262; T 262), ORR was higher with M (22%; 95% CI, 17.3-27.7%) vs T (16%; 95% CI 11.8-21.0%). Safety profiles were comparable in 529 pts who received study therapy. Grade ≥3 AEs and serious AEs occurred in 138 (52%) and 39 (15%) vs 128 (48%) and 46 (17%) pts on M vs T, respectively. PFS data cutoff: 10/10/18. Conclusions: In combination with chemotherapy in pretreated HER2+ MBC, M improves PFS over T with comparable safety. CD16A genotyping suggests a differential benefit in patients with a 158F allele. OS data are maturing. Clinical trial information: NCT02492711
2. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥ 2 HER2-directed regimens: Findings from the multinational, randomized, phase III NALA trial.