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

Wu,Wen-Shuo; Chen,Yuh-Min; Tsai,Chun-Ming; Shih,Jen-Fu; Chiu,Chao-Hua; Chou,Kun‑Ta; Lai,Shinn-Liang; Wu,Chieh-Hung; Luo,Yung-Hung; Huang,Chu‑Yun; Lee,Yu-Chin; Perng,Reury-Perng; Whang-Peng,Jacqueline

doi:10.3892/etm.2011.383

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

Authors:
- Wen-Shuo Wu
- Yuh-Min Chen
- Chun-Ming Tsai
- Jen-Fu Shih
- Chao-Hua Chiu
- Kun‑Ta Chou
- Shinn-Liang Lai
- Chieh-Hung Wu
- Yung-Hung Luo
- Chu‑Yun Huang
- Yu-Chin Lee
- Reury-Perng Perng
- Jacqueline Whang-Peng
View Affiliations

Affiliations: Chest Department, Taipei Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C., CECR, School of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
Published online on: November 16, 2011 https://doi.org/10.3892/etm.2011.383
Pages: 207-213

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1.	DM ParkinF BrayJ FerlayGlobal cancer statisticsCA Cancer J Clin5574108200510.3322/canjclin.55.2.74
2.	N ThatcherA ChangP ParikhGefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)Lancet36615271537200510.1016/S0140-6736(05)67625-8
3.	FA ShepherdPJ RodriguesT CiuleanuErlotinib in previously treated non-small-cell lung cancerN Engl J Med353123132200510.1056/NEJMoa05075316014882
4.	A ChangP ParikhS ThongprasertGefitinib (IRESSA) in patients of Asian origin with refractory advanced non-small cell lung cancer: Subset analysis from the ISEL studyJ Thorac Oncol1847855200610.1097/01243894-200610000-0001417409969
5.	ES KimV HirschT MokGefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trialLancet37218091818200810.1016/S0140-6736(08)61758-419027483
6.	TS MokY-L WuS ThongprasertGefitinib or carboplatin-paclitaxel in pulmonary adenocarcinomaN Engl J Med361947957200910.1056/NEJMoa081069919692680
7.	R RosellT MoranC QueraltScreening for epidermal growth factor receptor mutations in lung cancerN Engl J Med361958967200910.1056/NEJMoa090455419692684
8.	C ZhouYL WuG ChenEfficacy results from the randomized phase III OPTIMAL (CTONG 0802) study comparing first-line erlotinib versus carboplatin (CBDCA) plus gemcitabine (GEM), in Chinese advanced non-small-cell lung cancer (NSCLC) patients (PTS) with EGFR activating mutationsAnn Oncol21Suppl 8LBA132010
9.	YM ChenJ Whang-PengCM ChenReview of first-line systemic therapy for metastatic non-small cell lung cancerJ Exp Clin Med3116120201110.1016/j.jecm.2011.04.008
10.	PA JanneBE JohnsonEffect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitorsClin Cancer Res12Suppl 1444164420200610.1158/1078-0432.CCR-06-0555
11.	T KosakaY YatabeH EndohMutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implicationsCancer Res6489198923200410.1158/0008-5472.CAN-04-2818
12.	H ShigematsuL LinT TakahashiClinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancersJ Natl Cancer Inst97339346200510.1093/jnci/dji05515741570
13.	J BaselgaD RischinM RansonPhase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor typesJ Clin Oncol2042924302200210.1200/JCO.2002.03.100
14.	RS HerbstAM MaddoxML RothenbergSelective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trialJ Clin Oncol2038153825200210.1200/JCO.2002.03.038
15.	M HidalgoLL SiuJ NemunaitisPhase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignanciesJ Clin Oncol1932673279200111432895
16.	SV SharmaDW BellJ SettlemanEGFR growth factor mutations in lung cancerNat Rev Cancer7169181200710.1038/nrc2088
17.	WC FanCJ YuCM TsaiDifferent efficacies of erlotinib and gefitinib in Taiwanese patients with advanced non-small cell lung cancer: a retrospective multi-center studyJ Thor Oncol6148155201110.1097/JTO.0b013e3181f77b2721107294
18.	T CiuleanuL StelmakhS CicenasErlotinib versus docetaxel or pemetrexed as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC) and poor prognosis: efficacy and safety results from the phase III TITAN studyChicago Multidisciplinary Symposium in Thoracic Oncol: LBOA52010
19.	L VamvakasS AgelakiNK KentepozidisPemetrexed (MTA) compared with erlotinib (ERL) in pretreated patients with advanced non-small cell lung cancer (NSCLC): results of a randomized phase III Hellenic Oncology Research Group trialProc ASCO2875192010
20.	P TherasseSG ArbuckEA EisenhauerNew guidelines to evaluate the response to treatment in solid tumors. European Organisation for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of CanadaJ Natl Cancer Inst92205216200010.1093/jnci/92.3.205
21.	TJ LynchDW BellR SordellaActivating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinibN Engl J Med35021292139200410.1056/NEJMoa04093815118073
22.	JG PaezPA JanneJC LeeEGFR mutations in lung cancer: correlation with clinical response to gefitinib therapyScience30414971500200410.1126/science.109931415118125
23.	JD MoyerEG BarbacciKK IwataInduction of apoptosis and cell cycle arrest by OSI-774, an inhibitor of epidermal growth factor receptor tyrosine kinaseCancer Res574838484819979354447
24.	VA PolackDM SavageDA BakerInhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinoma with OSI-774: dynamics of receptor inhibition in situ and antitumor effects in athymic miceJ Pharmacol Exp Ther2917397481999
25.	BC ChoCK ImMS ParkPhase II study of erlotinib in advanced non-small cell lung cancer after failure of gefitinibJ Clin Oncol2525282533200710.1200/JCO.2006.10.416617577030
26.	SV SharmaDW BellJ SettlemanEpidermal growth factor receptor mutations in lung cancerNat Rev Cancer7169181200710.1038/nrc208817318210
27.	J GandhiJ ZhangY XieAlterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell linesPLoS One4e4576200910.1371/journal.pone.000457619238210
28.	CQ ZhuGC SantosK DingRole of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21J Clin Oncol2642684275200810.1200/JCO.2007.14.892418626007
29.	F CappuzzoT CiuleanuL StelmakhErlotinib as maintenance treatment in advanced non-small cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 studyLancet Oncol11521529201010.1016/S1470-2045(10)70112-120493771