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Sherrill B.,RTI Health Solutions | Di Leo A.,Sandro Pitigliani Medical Oncology Unit | Amonkar M.M.,Collegeville | Wu Y.,RTI Health Solutions | And 4 more authors.
Current Medical Research and Opinion | Year: 2010

Background: In a phase 3 randomized, multicenter, double-blind, placebo-controlled study, first-line therapy with lapatinib plus paclitaxel significantly improved clinical outcomes based on a pre-planned analysis of ErbB2 metastatic breast cancer patients (GSK Study #EGF30001; ClinicalTrials.gov identifier: NCT00075270). Patients with ErbB2-or untested did not significantly benefit. This article focuses on the quality of life (QOL) and quality-adjusted survival outcomes (Q-TWiST) in the study. Methods: QOL was assessed using the Functional Assessment of Cancer TherapyBreast (FACT-B). Changes from baseline were analyzed using ANCOVAs, repeated measures and pattern mixture modeling. The Q-TWiST method was used to examine the trade-off between toxicities and delayed progression. Results: The study included 579 subjects, of whom 86 were ErbB2. In the ITT population, no significant differences in QOL or Q-TWiST scores were observed. In the ErbB2 subgroup, the lapatinib plus paclitaxel (LP) arm demonstrated stable FACT-B scores over the first year, while average scores for patients on Pplacebo (Ppla) monotherapy decreased (change from baseline: LP, p=0.99; Ppla, p=0.01). Clinically meaningful differences were observed between treatment arms on the FACT-B, Trial Outcome Index and breast cancer subscale scores. Pattern mixture models suggested more QOL differentiation between treatments among patients who progressed or withdrew early. Q-TWiST differences between the arms in the ErbB2 subgroup ranged from 2 to 15 weeks with an LP advantage across all utility weight combinations. Conclusions: In the ITT population, results provide no evidence of QOL differences between treatment groups. In a small, prospectively-defined subgroup of ErbB2 patients, LP resulted in more stable QOL and more quality-adjusted survival than paclitaxel monotherapy, representing clinically important differences between treatments. © 2010 Informa UK Ltd All rights reserved.

Downey L.,Arizona Cancer Center | Livingston R.B.,Arizona Cancer Center | Koehler M.,Glaxosmithkline | Arbushites M.,Glaxosmithkline | And 6 more authors.
Clinical Cancer Research | Year: 2010

Purpose: It has been suggested that a subgroup of human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with chromosome 17 (Chr-17) polysomy benefit from HER2-directed therapy. This hypothesis was examined using the data from a phase III trial that randomized patients with HER2-negative or HER2-untested metastatic breast cancer to first-line therapy with paclitaxel along with either lapatinib or placebo. Experimental Design: HER2 expression level by immunohistochemistry, fluorescence in situ hybridization (FISH), and mean HER2 ratio of Chr-17 values were determined centrally using archival tissue. Polysomy means of 2.0 and 2.2 served as thresholds. Results: Of 580 patients on the original trial, 406 were HER2 negative by FISH. Progression-free survival (PFS) data were available for 405 patients, of whom 44 (11%) met the definition of polysomy (Chr-17 ≥2.2, FISH negative for HER2). Median PFS in the polysomy group was 20.9 and 24.4 weeks for paclitaxel plus lapatinib and paclitaxel plus placebo, respectively. In the nonpolysomy group, median PFS was 24.6 and 23.1 weeks for paclitaxel plus lapatinib and paclitaxel plus placebo, respectively. Log-rank testing showed no treatment advantage for either group. Similar results were found using a Chr-17 polysomy cutoff of 2.0. Response rates in the polysomy group were 17% for paclitaxel plus lapatinib and 10% for paclitaxel plus placebo. In the nonpolysomy group, response rates were 32% for paclitaxel plus lapatinib and 25% for paclitaxel plus placebo. Neither comparison was statistically significant. Conclusion: This analysis could not confirm the hypothesis that Chr-17 polysomy in HER2-nonamplified patients improved chemotherapy outcome when lapatinib is added as a HER2-targeted treatment. ©2010 AACR.

Partridge A.H.,Dana-Farber Cancer Institute | Rumble R.B.,American Society of Clinical Oncology | Carey L.A.,University of North Carolina at Chapel Hill | Come S.E.,Beth Israel Deaconess Medical Center | And 10 more authors.
Journal of Clinical Oncology | Year: 2014

Recommendations: Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary (eg, immediately life-threatening disease). Single agent is preferable to combination chemotherapy, and longer planned duration improves outcome but must be balanced against toxicity. There is no single optimal first-line or subsequent line chemotherapy, and choice of treatment will be determined by multiple factors including prior therapy, toxicity, performance status, comorbid conditions, and patient preference. The role of bevacizumab remains controversial. Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer.Methods: A systematic review of randomized evidence (including systematic reviews and meta-analyses) from 1993 through to current was completed. Outcomes of interest included survival, progressionfree survival, response, quality of life, and adverse effects. Guideline recommendations were evidence based and were agreed on by the Expert Panel via consensus.Purpose: To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)-negative (or unknown) advanced breast cancer.Results: Seventy-nine studies met the inclusion criteria, comprising 20 systematic reviews and/or metaanalyses, 30 trials on first-line treatment, and 29 trials on second-line and subsequent treatment. These trials form the evidence base for the guideline recommendations. © 2014 by American Society of Clinical Oncology.

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