Lapatinib minimally effective for non-small-cell lung cancer
" f5 ], L( o1 |2 |1 |MARCH 18, 2010 P' X" |$ W: X! `6 a8 Z a* c
" b o" L4 u8 U8 ]. K3 pNEW YORK (Reuters Health) - Although well tolerated, lapatinib is minimally effective as monotherapy for advanced or metastatic non-small-cell lung cancer (NSCLC), according to a report in the March 15th Clinical Cancer Research.
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Lapatinib (GlaxoSmithKline) is a tyrosine kinase inhibitor of both epidermal growth factor receptor (EGFR) and HER2, the authors explain, and thus has theoretical advantages over inhibition of either EGFR or HER2 alone.
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Dr. Helen J. Ross, from Mayo Clinic, Scottsdale, Arizona, and colleagues evaluated the overall response rate to lapatinib in 131 patients with advanced or metastatic NSCLC. Sixty-five patients were randomized to lapatinib 1500 mg once daily and 66 to lapatinib 500 mg twice daily.$ b* h8 o$ n" s& x- _0 v
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When the study began, patients with any type of advanced or metastatic NSCLC were recruited ("non-targeted" population). However, when data from other studies began to show that EGFR inhibitors are particularly effective in patients with bronchioloalveolar carcinoma and in never-smokers with any histology of NSCLC, recruitment began to "target" such patients.
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6 x, G# a4 G4 m; |, hThe targeted population included 24 patients in the 1500 mg/day group and 32 in the 500 mg twice daily group. The corresponding numbers in the non-targeted population were 41 and 34.: O2 {6 S) E; n# E0 @
7 t/ K0 I5 ?) _ W- pAt the interim analysis of the first 30 targeted patients to reach the initial response evaluation, the response rate was 0% in both treatment groups. In the non-targeted population, one patient in the 1500-mg group achieved a partial response. % ` q3 I' c: L
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Overall, 31 of 131 patients (24%) had stable disease or better.
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. U. ?2 x/ X; ?Based on these findings, the study was stopped for reasons of futility, the investigators state. 9 ` N$ {! A; _- ?% q" w {* C6 W
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Overall survival in the targeted population was 15.2 months for the 1500-mg once-daily group and 13.9 months for the 500-mg twice-daily group, and in the nontargeted population, overall survival was 11.4 months for the 1500-mg once-daily group and 8.1 months for the 500-mg twice-daily group.
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/ }% ~0 z8 W- F2 `# r6 o4 gMedian progression-free survival was 15.6 weeks (1500-mg once-daily) and 8.7 weeks (500-mg twice-daily) in the targeted population and 12.0 weeks (1500-mg once-daily) and 8.6 weeks (500-mg twice-daily) in the nontargeted population.
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The incidence of adverse events considered to be related to study medication was 89% for 1500 mg once daily and 83% for 500 mg twice daily, but only 8% of patients in each group experienced serious adverse events related to study medication.
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Among 92 patients with tumor tissue available, 2 had mutations in EGFR and 1 had mutations in both EGFR and KRAS. None had mutations in HER2. ; b% D7 e/ G( r
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Of 77 patients with sufficient DNA for gene copy evaluation, 5 (8.8%) had increased EGFR copy number and 2 (3.5%) had increased HER2 gene copy number. # d- Y5 C) @$ u5 ?
- C9 e% s( u E7 S4 q0 B u. z( nNone of the patients with EGFR mutations responded to lapatinib, and only 1 patient with HER2 amplification had an unconfirmed decrease of 51% in tumor measurement.
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"Lapatinib as a single agent at the doses studied seems to have minimal single-agent activity, at least as measured by response rates," the authors conclude, "although progression-free survival in the 1500-mg once-daily group was in the range that would be expected with first-line chemotherapy."
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; A0 X) I9 Q# ^) ~' g( y" Y"Patients in this small study had a suggestion of disease stabilization with lapatinib," Dr. Ross said. "It would be of interest to examine it in the adjuvant setting after resection perhaps, after chemoradiotherapy perhaps or after up-front chemotherapy. It is possible that combination with other targeted agents, such as anti-angiogenic agents, might be useful."
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The study was sponsored by GlaxoSmithKline.. C: y7 R6 A% d1 D0 y% u' o7 c
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