Neratinib Has Limited Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer
, }9 l# G9 f1 G0 Y9 UGENEVA -- October 23, 2008 -- Neratinib (HKI-272) is well tolerated and shows limited efficacy in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with erlotinib/gefitinib treatment, according to results of a 3-arm, phase 2 study.
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Erlotinib and gefitinib can provide dramatic responses in patients with NSCLC, although virtually all of these patients eventually develop progressive disease. Earlier research demonstrated that patients with advanced NSCLC who received prior gefitinib or erlotinib treatment had stable disease after treatment with neratinib.
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The T790M epidermal growth factor receptor (EGFR) gene mutation can confer resistance to erlotinib and gefitinib. Neratinib is an EGFR inhibitor and is active against the T790M mutation. Therefore, researchers tested this compound in patients who received at least 12 weeks of erlotinib or gefitinib.6 R4 N3 ?3 Z$ L! z0 T
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The results of this study were presented here at the 20th International Symposium of the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR).
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Investigator Benjamin Besse, MD, PhD, Department of Medicine, Gustave Roussy Institute, Villejuif, France, discussed results in a poster session on October 22.& Q) G5 I1 a: O( t. I, |% O
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The primary endpoint was objective response rate (ORR), defined as complete plus partial responses. Secondary endpoints included safety, clinical benefit rate, duration of response, and progression-free survival.
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6 {. J; `7 [. l/ {A total of 167 patients (median age, 60 years; male, 29%) were divided into 3 groups: arm A, progression after >=12 weeks of erlotinib or gefitinib treatment and tumour positive for EGFR mutation (n = 91); arm B, progression after >=12 weeks of erlotinib or gefitinib treatment and tumour negative for EGFR mutation (n = 48); and arm C, no prior EGFR tyrosine kinase inhibitor treatment, adenocarcinoma, <=20 pack-year smoker and current nonsmoker, and tumour positive or negative for EGFR mutation (n = 28).
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Neratinib was administered orally initially at 320 mg daily, later reduced to 240 mg by protocol amendment after gastrointestinal adverse effects were reported. Efficacy evaluation was done according to the Response Evaluation Criteria in Solid Tumours (RECIST) classification.6 X5 L. m+ q1 m, b% ]- X' e
5 t6 h# u! O0 s& {$ kResults show no significant differences in ORR across the treatment arms: arm A, 2%; arm B, 2%; and arm C, 4%. The same was seen for patients with stable disease (47%, 46%, and 39%, respectively); for progression-free survival (11.6, 14.7, and 7.4 weeks, respectively); and for clinical benefit rates at 16 weeks (24%, 19%, and 36%, respectively).% R8 S/ L, L8 ~) \- x4 B% L
: N% I) ?! A0 r$ l4 i' L# _, kAlthough neratinib did provide apparent limited efficacy in these patients with NSCLC, Dr. Besse indicated that the molecular characteristics and prior erlotinib/gefitinib treatment variables did not correlate with neratinib efficacy.! b/ F# p+ k$ c) o! w8 C, B* h$ M
1 Z+ U5 a$ H+ \, q9 d& QDr. Besse explained, "We were expecting more activity in the erlotinib/gefitinib arm than we saw ... and one of the explanations for this is probably based on the tumour profile, as [from the biopsy to the analysis] the patients received platinum-based therapy for at least 12 weeks."
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