Lapatinib minimally effective for non-small-cell lung cancer V) q- e6 Y8 t9 g' d
MARCH 18, 2010
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NEW 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., [, X4 s: n* M, T& x8 c) N0 v/ u
0 @5 @2 c1 \: x. J, n8 w8 NLapatinib (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.
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0 O! n5 T; B3 k" ~: J( j0 O! y6 w5 [- TWhen 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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9 I0 p7 V# y8 E* y- r9 f3 L1 VThe 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.
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At 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. ) L y7 [- X( h. t/ W/ P; H V- t
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Overall, 31 of 131 patients (24%) had stable disease or better.
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Based on these findings, the study was stopped for reasons of futility, the investigators state. % }6 d4 S0 T) \/ m
% q5 I4 V) q* ~* F; R. c/ UOverall 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. 9 [( [6 }: v0 A P
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Median 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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* n. O, _" r. X$ q$ {& M' }. f/ kThe 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. $ ^7 m: N5 ?0 g8 u* m1 p% n
& e# Z& P2 A8 V% u4 m) U o, V: rAmong 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. ! k* Y4 ~" ?$ x0 D% d1 [* Y5 q
2 v2 o$ Q& T$ C6 f* ^6 iOf 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.
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: U+ U8 f' U/ }- F! i: @$ g7 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. 6 J# [) {5 s n: O
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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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"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." + K0 r& ~9 \! J/ ]
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The study was sponsored by GlaxoSmithKline.
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