Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations

Abstract

Abstract. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are an effective treatment for advanced non-small cell lung cancer. The objective of the present study was to compare the efficacy of gefitinib and erlotinib in patients with pulmonary adenocarcinoma, whose tumor EGFR mutation status was known. Pulmonary adenocarcinoma patients who began receiving gefitinib or erlotinib treatment from January 2005 to December 2010, and whose tumor EGFR mutation status had been determined, were included. Clinical data, type of treatment response and survival time data were collected. Of the 224 patients enrolled, 124 received gefitinib treatment and 100 received erlotinib treatment. Of these patients, 146 individuals had tumors with EGFR-activating mutations (exon 19 deletions and/point mutation of L858R in exon 21) and 78 did not. There was no difference in treatment response whether or not the patients had tumors with EGFR-activating mutations at the time they received gefitinib or erlotinib treatment. The median progression-free survival (PFS) of the gefitinib and erlotinib groups was 7.6 and 7.9 months, respectively (p=0.4731). PFS was significantly longer for patients without EGFR-activating mutations who received erlotinib treatment (n=48; median, 4.5 months) than for those who received gefitinib treatment (n=30; median, 2.3 months), with a hazard ratio of 0.58 (95% CI, 0.35-0.96; p=0.0339). Patients whose tumors had EGFR-activating mutations displayed no difference in PFS with either gefitinib (n=94; median, 10.5 months) or erlotinib treatment (n=52; median, 10.4 months). In conclusion, PFS showed no difference with either agent in patients whose tumors had EGFR-activating mutations, but was significantly longer in patients whose tumors did not have EGFR-activating mutations when receiving erlotinib treatment. IntroductionWorldwide, lung cancer is the leading cause of cancer mortality (1). Major progression in understanding molecular cancer biology and in determining the mechanisms of oncogenesis during the last decade has resulted in the development of molecular targets for non-small cell lung cancer (NSCLC) treatments. Inhibition of the epidermal growth factor receptor (EGFR) pathway with tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, provides an effective and promising treatment for NSCLC, as either first-line or salvage therapy, with the added advantage of improved efficacy, tolerability and quality of life compared with other chemotherapy agents (2-9). It has been demonstrated that a subset of patients (female, never smoked, East Asian with an adenocarcinoma diagnosis) may respond better to EGFR-TKIs. A higher prevalence of sensitive EGFR-activating mutations (deletion in exon 19 or point mutation of L858R in exon 21) has been found in this subset of patients (10-12).Gefitinib and erlotinib were each compared with a placebo in phase III randomized trials (ISEL and BR.21, respectively) in which the majority of enrolled patients were Caucasian (2,3). The varying overal...

Gefitinib: a review of its use in adults with advanced non-small cell lung cancer

“…In addition to these studies, several retrospective registry studies showed similar efficacy of gefitinib and erlotinib in patients with advanced/metastatic or recurrent NSCLC [92,93] or stage IIIB or IV pulmonary adenocarcinoma [94]. Furthermore, a recent network meta-analysis indirectly compared the efficacy of gefitinib, erlotinib, icotinib and afatinib and showed that the four agents had generally similar efficacy in patients with NSCLC and activating EGFR mutations [95].…”

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation testing in adults with locally advanced or metastatic non-small cell lung cancer: a systematic review and cost-effectiveness analysis

“…This study included 224 patients, with known tumour EGFR mutation status, who had received TKI treatment (124 gefitinib and 100 erlotinib) but was not restricted to first-line treatment; no significant difference between the two treatments was observed for either PFs or OR rate. 77 …”

Comparison is beyond IPASS and OPTIMAL

“…More treatment-related grade-3 or -4 adverse events were observed with erlotinib versus gefitinib (12.4% vs 4.2%). Wu et al 10 conducted a retrospective study to evaluate the difference in efficacy between erlotinib and gefitinib in Taiwanese patients with advanced-stage EGFR mutation-positive NSCLC. They also found no statistically significant difference in response rate and PFS between the two drugs.…”