Lapatinib minimally effective for non-small-cell lung cancer$ _! J8 q/ |" L/ F, u9 d5 d& Y, M7 C
MARCH 18, 2010
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: p( V" S. c& E. s. v; @& |) d7 xNEW 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.1 S O2 E9 @" j) O5 o5 B
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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.1 \+ m' r7 ^- j
9 F3 W' S: A2 ^& }. I5 X0 aThe 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., M. q1 I+ C# N x, K: V4 M) n
: W! y: K6 G2 hAt 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.
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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. ) Y/ q: o! N3 G! M& z& F9 V
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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. , t; j* V0 v5 u. D
6 I$ Y) w4 y" p" L+ R" ZMedian 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. " v1 a/ n! L+ I' |' l4 q3 b" P
8 R/ f9 f! w# B6 s( p5 h; ^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. # ^& Q1 j Z7 c9 H
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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.
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8 d/ R8 S$ ~0 T) HOf 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. 5 O3 R# E' U) e- s' j5 }
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None 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. 2 Y$ u* a& C O. {) B. n6 |" e
! _' l$ c$ _. B( Y/ ~"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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& v" i/ P6 Y/ ~; |3 d, i- E"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." 3 C9 k. h. `5 K+ ^
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The study was sponsored by GlaxoSmithKline.
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