Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919.

Breast Cancer - HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer - HER2/ER
Abstract Number: 


Karen A. Gelmon, Frances Boyle, Bella Kaufman, David Huntsman, Alexey Manikhas, Angelo Di Leo, Miguel Martin, Lee Steven Schwartzberg, Susan Faye Dent, Susan Ellard, Katia Sonia Tonkin, Yasir M. Nagarwala, Kathleen I. Pritchard, Timothy Joseph Whelan, Dora Nomikos, Judy-Anne W. Chapman, Wendy Parulekar; British Columbia Cancer Agency-Vancouver Cancer Centre, Vancouver, BC, Canada; Mater Hospital, North Sydney, Australia; Chaim Sheba Medical Center, Tel Hashomer, Israel; British Columbia Cancer Agency, Vancouver, BC, Canada; City Clinical Oncological Dispensary, St. Petersburg, Russia; Sandro Pitigliani Medical Oncology Unit, Prato, Italy; Hospital Universitario Gregorio Maranon, Madrid, Spain; The West Clinic, Memphis, TN; The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada; Cancer Centre for Southern Interior, Kelowna, BC, Canada; Cross Cancer Institute, Edmonton, AB, Canada; GlaxoSmithKline Oncology, Collegeville, PA; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON, Canada; NCIC Clinical Trials Group, Kingston, ON, Canada; NCIC Clinical Trials Group, Queen's University, Kingston, ON, Canada

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Abstract Disclosures


Background: The relative efficacy of L vs T when combined with Tax chemotherapy in the first-line setting of metastatic breast cancer (BC) is unknown. Methods: MA.31 compares Tax-based therapy, paclitaxel 80mg/m2 wkly or docetaxel 75mg/m2 3 wkly for 24 wks in combination with L or T. The L dose was 1,250 mg po daily with Tax followed by 1,500 mg daily (LTax/L). After a loading dose, the T dose was 2 mg/kg wkly or 6 mg/kg 3 wkly + Tax followed by T 6 mg/kg 3 wkly (TTax/T). Stratification was by prior neo/adjuvant HER2 therapy, prior neo/adjuvant Tax, planned Tax (paclitaxel vs docetaxel), and liver metastases. The primary endpoint is ITT progression-free survival (PFS), defined as time from randomization to objective progressive disease based on RECIST criteria or death from any cause. The protocol-specified IA was performed after observing 333 PFS events; the trial was to stop if the 2-sided p-value from the stratified log-rank test was less than 0.03. The NCIC CTG’s independent DSMC reviewed IA results and recommended disclosure because the superiority boundary was crossed. A secondary analysis utilized central laboratory-confirmed HER2 + status. Results: Between July 17 2008 and Dec 1 2011, 652 pts were accrued. Data from 636 pts (525 HER2 centrally confirmed) were included in the IA with clinical cutoff date of Nov 7 2011 and database lock of Apr 13 2012. Median follow-up was 13.6 mos, 12.9 mos for LTax/L pts and 14.0 mos for TTax/T patients. In the ITT analysis, PFS was inferior with LTax/L compared to TTax/T hazard ratio (HR) =1.33; 95% CI 1.06-1.67; p=0.01. LTax/L had median PFS 8.8 mos (95% CI 8.3-10.6) compared to TTax/T 11.4 mos (95% CI 10.8-13.7). PFS in the centrally confirmed HER2+ had HR 1.48 (95%CI 1.15-1.92; p=0.003) (LTax/L to TTax/T). No difference in overall survival was detected (LTax/L to TTax/T) HR= 1.1 (95% CI 0.75-1.61; p=0.62). More grade 3-4 diarrhea and rash was observed with LTax/L (p<0.001). Conclusions: LTax/L therapy is associated with a shorter PFS compared to TTax/T as first line therapy for HER2+ metastatic BC. ClinicalTrials.gov: NCT00667251. CCSRI grant: 021039. Supported by GlaxoSmithKline.