Lapatinib (L) with paclitaxel compared to paclitaxel as first-line treatment for patients with metastatic breast cancer: A phase III randomized, double-blind study of 580 patients
2007; Lippincott Williams & Wilkins; Volume: 25; Issue: 18_suppl Linguagem: Inglês
10.1200/jco.2007.25.18_suppl.1011
ISSN1527-7755
AutoresAngelo Di Leo, Henry Gómez, Zeba Aziz, Zanete Zvirbule, Michael Arbushites, Cristina Oliva, María Koehler, L. S. Williams, Judy Dering, RS Finn,
Tópico(s)Advanced Breast Cancer Therapies
Resumo1011 Background: L is an oral tyrosine kinase inhibitor of EGFR/HER2, active as monotherapy and in combination for HER2-overexpressing advanced/metastatic breast cancer (BC). A Phase I study of L with paclitaxel (P) indicated no unexpected adverse events (AEs). PK profile indicated no relationship between peak plasma concentration of P+L and neuropathy, neutropenia, diarrhea, rash or myalgia. We report here blinded efficacy and safety data for patients (pts) with incurable Stage IIIb/IIIc/IV BC at first diagnosis or relapse, untested or negative (0/1+ IHC or FISH neg) for HER2. Unblinded data will be presented at ASCO 2007. Methods: Between Jan 2004 and Jul 2005, 580 pts from 24 countries were stratified by metastatic site and randomized 1:1 to L 1500 mg QD + 175 mg/m 2 P q3w or placebo QD + 175 mg/m 2 P q3w. Primary endpoint was TTP; secondary endpoints were AEs, ORR, PFS, CBR, RFS, and OS. Tumor tissue was obtained from the most recent biopsy of 451 (78%) pts and was centrally analyzed in blinded fashion for biomarker patterns. Serum samples were collected for central EGFR and HER2 ECD analysis. Results and Conclusions: 579 pts were analyzed; 87% presented with Stage IV BC. 55% received prior adjuvant chemotherapy or anti-hormonal therapy. No pts received previous trastuzumab. At the time of analysis, 561 (97%) pts progressed or otherwise withdrew. Most common AEs were alopecia (58%), neurological (55%, gr=3:8%), diarrhea (42%, gr=3:9%), nausea (32%), and rash (32%, gr=3:2%). Neutropenia and thrombocytopenia AEs related to study treatment were 18% and <1%, respectively. LVEF decrease of 20% relative to baseline and below LLN was reported 15 times. 12% of AEs led to treatment withdrawal. Blinded data analysis revealed a median TTP of 25 wks and ORR of 30%. CNS relapse was reported in 11 pts (2%). Enrollment predominantly came from countries with limited HER2 testing capacity thus a subgroup of pts is expected to be HER2+ve. Blinded analyses of HER2, ER and PR are ongoing at this time and final biomarker evaluations will be presented with unblinded efficacy data. [Table: see text]
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