Document Detail

Randomized phase II multicenter trial of two schedules of lapatinib as first- or second-line monotherapy in patients with advanced or metastatic non-small cell lung cancer.
MedLine Citation:
PMID:  20215545     Owner:  NLM     Status:  MEDLINE    
PURPOSE: This randomized phase II study was initially designed to test the activity of two dose schedules of lapatinib (GW572016H), an oral, reversible, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2/neu; HER2), in chemotherapy-naive patients with non-small cell lung cancer (NSCLC); it was later amended to target patients with bronchioloalveolar carcinoma or no smoking history.
EXPERIMENTAL DESIGN: Patients with good performance status and recurrent or metastatic NSCLC were randomized to lapatinib (orally, 1,500 mg once daily or 500 mg twice daily) until progression or intolerance. Patients could have had a maximum of one prior systemic therapy (chemotherapy or biological therapy) for NSCLC. Safety and activity were assessed every 4 and 8 weeks, respectively. Tumors were analyzed for EGFR and HER2 mutations and/or amplifications.
RESULTS: Of 75 patients in the nontargeted population, 1 (1.3%) had partial response and 16 (21%) had stable disease of >or=24 weeks. No complete or partial responses were observed in 56 patients in the targeted population; 14 (25%) had stable disease of >or=24 weeks. No responses were seen in three patients with EGFR mutations and five with EGFR gene amplification. No mutations in HER2 were found. One of two patients with HER2 amplification had a 51% decrease in tumor size; however, this response was unconfirmed. The most common adverse events were grade 1 or 2 diarrhea, rash, fatigue, nausea, and anorexia. Adverse events were similar across dosing regimens.
CONCLUSIONS: Lapatinib was well tolerated, with no notable difference in toxicity between treatment groups. Lapatinib monotherapy did not induce a significant number of tumor regressions in NSCLC. Further studies may be warranted to determine whether lapatinib is active in combination with other agents in the treatment of NSCLC.
Helen J Ross; George R Blumenschein; Joseph Aisner; Nevena Damjanov; Afshin Dowlati; Jennifer Garst; James R Rigas; Michael Smylie; Habib Hassani; Kimberly E Allen; Lance Leopold; Tal Z Zaks; Frances A Shepherd
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-03-09
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  16     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-16     Completed Date:  2010-06-22     Revised Date:  2012-10-12    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1938-49     Citation Subset:  IM    
Mayo Clinic, Scottsdale, Arizona 85259, USA.
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MeSH Terms
Adenocarcinoma / drug therapy,  pathology
Adenocarcinoma, Bronchiolo-Alveolar / drug therapy,  pathology
Aged, 80 and over
Antineoplastic Agents / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy*,  pathology
Carcinoma, Squamous Cell / drug therapy,  pathology
Drug Resistance, Neoplasm
Lung Neoplasms / drug therapy*,  pathology
Middle Aged
Neoplasm Metastasis
Neoplasm Recurrence, Local / drug therapy*,  pathology
Quinazolines / therapeutic use*
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  metabolism
Receptor, erbB-2 / antagonists & inhibitors,  metabolism
Salvage Therapy
Survival Rate
Treatment Outcome
Reg. No./Substance:
0/Antineoplastic Agents; 0/Quinazolines; 0/lapatinib; EC protein, human; EC protein, human; EC, Epidermal Growth Factor; EC, erbB-2

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