2019 ASCO Annual Meeting!
Session: Plenary Session Including the Distinguished Achievement Award and Science of Oncology Award Lecture
Type: Plenary Session
Time: Sunday June 2, 1:00 PM to 4:00 PM
Location: Hall B1
ANNOUNCE: A randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) + olaratumab versus dox + PBO in patients (pts) with advanced soft tissue sarcomas (STS).
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr LBA3)
Author(s): William D. Tap, Andrew J. Wagner, Zsuzsanna Papai, Kristen N. Ganjoo, Chueh-Chuan Yen, Patrick Schoffski, Albiruni Ryan Abdul Razak, Javier Martin Broto, Alexander I. Spira, Akira Kawai, Anders Krarup-Hansen, Axel Le Cesne, Brian Van Tine, Yoichi Naito, Se Hoon Park, Victoria Soldatenkova, Gary Mo, Ashwin Shahir, Jennifer Wright, Robin Lewis Jones; Memorial Sloan Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Allami Egeszsegugyi Kozpont (State Health Center), Budapest, Hungary; Stanford Cancer Institute, Stanford, CA; Taipei Veterans General Hospital, Taipei, Taiwan; Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Princess Margaret Hospital, Toronto, ON, Canada; Virgen del Rocio University Hospital, Institute of Biomedicine Research (IBIS)/CSIC/Universidad de Sevilla, Seville, Spain; Virginia Cancer Specialists, Fairfax, VA; National Cancer Center Hospital, Tokyo, Japan; University Hospital Cophenhagen, Cophenhagen, Denmark; Gustave Roussy Cancer Campus, Villejuif, France; Washington University in Saint Louis, Saint Louis, MO; National Cancer Center Hospital East, Kashiwa, Japan; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; European Statistics, Oncology, Lilly Deutschland GmbH, Bad Homburg, Germany; Eli Lilly and Company, Indianapolis, IN; Eli Lilly and Company, Erl Wood, United Kingdom; University of Utah, Salt Lake City, UT; Royal Marsden Hospital, The Institute of Cancer Research, London, United Kingdom
Background: Dox is standard therapy in STS. In a Ph 2 trial, olaratumab (a human IgG1 antibody targeting PDGFRα) + dox improved overall survival (OS) and progression-free survival (PFS) vs dox. ANNOUNCE aimed to confirm the OS benefit in advanced STS. Methods: Adult pts with unresectable locally advanced or metastatic STS, anthracycline-naïve, and ECOG PS 0-1 were eligible. Pts were randomized 1:1 to olaratumab (20mg/kg Cycle 1, 15mg/kg subsequent cycles) or PBO on Days 1 and 8 of each 21-day cycle combined with dox (75mg/m2) on Day 1 for up to 8 cycles. After 8 cycles, pts with disease control continued olaratumab or PBO until progression or toxicity. Randomization was stratified by histology, prior systemic therapy, ECOG PS, and geographic region. Dexrazoxane use was allowed to mitigate dox-related cardiotoxicity. Primary endpoints were OS in the intent-to-treat (ITT) population and/or leiomyosarcoma (LMS) subset of the ITT population; the study was designed to be positive if either primary endpoint was met. Secondary endpoints included PFS, response/disease control rates, safety, and pharmacokinetics. Results: 509 pts were randomized: 258 in the investigational and 251 in the control arm. Baseline pt characteristics were well balanced. Dexrazoxane was received by 63.0% vs 65.1% of pts (investigational vs control arm, respectively, for all data). In the ITT population, median OS was 20.4 vs 19.8 months (m) (HR=1.05, 95% CI: 0.84-1.30; p = 0.69) and was 21.6 vs 21.9 m in LMS pts (HR=0.95, 95% CI: 0.69-1.31; p = 0.76). Median PFS was lower in the investigational arm in the ITT population (5.4 vs 6.8 m; HR=1.23, 95% CI: 1.01-1.50; p = 0.04) and in LMS pts (4.3 vs 6.9 m, HR=1.22, 95% CI: 0.92-1.63; p = 0.17). Median dox exposure was 6 vs 7 cycles. Safety was similar between arms. Olaratumab serum concentrations reached levels expected from prior trials. Additional subgroup/biomarker results will be presented. Conclusions: ANNOUNCE did not confirm that olaratumab + dox, followed by olaratumab monotherapy, improves OS over dox in pts with advanced STS. Further analyses are warranted to explore the inconsistent outcomes between the Ph 3 and Ph 2 studies. Clinical trial information: NCT02451943
1. Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: Final results of a randomized clinical trial from the Italian Sarcoma Group, the Spanish Sarcoma Group (GEIS), the French Sarcoma Group (FSG), and the Polish Sarcoma Group (PSG).