Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy

Sunaga, Noriaki; Tomizawa, Yoshio; Yanagitani, Noriko; Iijima, Hironobu; Kaira, Kyoichi; Shimizu, Kimihiro; Tanaka, Shigebumi; Suga, Tatsuo; Hisada, Takeshi; Ishizuka, Tamotsu; Saito, Ryusei; Dobashi, Kunio; Mori, Masatomo

doi:10.1016/j.lungcan.2007.01.025

Cited by 125 publications

(76 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Table 1 summarizes the 5 identified Japanese-based studies. The characteristics of these EGFRmutant patients in these publications [43][44][45][46][47] were similar among the different studies. Most patients were women, nonsmokers and had adenocarcinomas ( Table 2).…”

Section: Identification Of Five Prospective Trials Of Patients With Esupporting

confidence: 53%

“…In only one of the trials did the exon 19 deletion cohort have a significantly higher response rate than the L858R patients, however even in that trial the investigators noted that the L858R patients with SD by RECIST had measurable tumor responses that did not qualify as PR [47]. Overall, in these prospectively collected patients the L858R patients were as likely as the exon 19 deletion ones to derived responses from gefitinib monotherapy.…”

Section: Response Rates In the Total Population And By Different Egfrmentioning

confidence: 98%

“…Based on our search criteria, we identified six reports that prospectively evaluated the effects of gefitinib monotherapy for advanced NSCLC based on the presence of an EGFR tyrosine kinase domain mutation in the patient's tumor specimens [43][44][45][46][47][48]. All trials were published between 2006 and 2007.…”

Section: Identification Of Five Prospective Trials Of Patients With Ementioning

confidence: 99%

See 2 more Smart Citations

Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers

et al. 2007

View full text Add to dashboard Cite

Purpose-Epidermal growth factor receptor (EGFR) mutations have been found in the majority of gefitinib-responsive non-small cell lung cancer (NSCLC) patients from retrospective studies. We sought to compile the available phase II and prospective trials of this EGFR tyrosine kinase inhibitor (TKI) to better understand the efficacy and safety of selecting patients to receive gefitinib based on their genotype.Design-We searched published trials involving EGFR-mutant patients and gefitinib. Five reports were identified (published between June 2006 and April 2007) in which gefitinib was given in a prospective manner to EGFR mutation positive patients at a dose of 250 mg a day. Responses were determined by RECIST and toxicities by NCI-CTC.Results-A total of 101 patients were pooled from these studies. 59 received gefitinib as their first line of therapy and 42 after having received chemotherapy. The combined rate of complete and partial response (CR+PR) in the 99 measured patients was 80.8% (80/99) and only 7.1% (7/99) had progressive disease as best response. The response rate (CR+PR) for exon 19 deletion and L858R patients were 80.3% (53/66) and 81.8% (27/33), respectively. The median progression-free survival ranged from 7.7 to 12.9 months. Overall survival had not been reached in 4/5 reports and was 15.4 months in one of them. Gefitinib administration was safe (<50% of patients developed grade 1-2 skin rash or diarrhea) and interstitial lung disease was only reported in 2 patients (2%), without deaths.Conclusions-Gefitinib monotherapy leads to objective responses in most patients with EGFR mutations. Both L858R and deletion 19 mutations derived similar clinical benefits. Small molecule TKIs are the new treatment paradigm for EGFR-mutant NSCLC.

show abstract

Section: Identification Of Five Prospective Trials Of Patients With Esupporting

confidence: 53%

Section: Response Rates In the Total Population And By Different Egfrmentioning

confidence: 98%

Section: Identification Of Five Prospective Trials Of Patients With Ementioning

confidence: 99%

See 1 more Smart Citation

Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers

et al. 2007

View full text Add to dashboard Cite

show abstract

“…(10)(11)(12)(13)(14) Indeed, we and others have prospectively demonstrated a high response rate to EGFR TKI therapy in NSCLC patients with EGFR mutations. (15)(16)(17)(18)(19)(20)(21) An increased copy number of the EGFR gene, as revealed by fluorescence in situ hybridization (FISH), has also emerged as an effective molecular marker of EGFR TKI sensitivity in NSCLC. (22)(23)(24) We previously showed that EGFR mutation and EGFR amplification are associated in human NSCLC cell lines and that endogenous EGFR expressed in such cell lines positive for both of these EGFR alterations are activated constitutively.…”

mentioning

confidence: 99%

Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non‐small cell lung cancer

et al. 2008

View full text Add to dashboard Cite

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with the response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Increased EGFR copy number has also been associated with sensitivity to these drugs. However, given that it is often difficult to obtain sufficient amounts of tumor tissue for genetic analysis from patients with advanced NSCLC, the relationship between these two types of EGFR alterations has remained unclear. We have now evaluated EGFR mutation status both by direct sequencing and with a high-sensitivity assay, the Scorpion-amplification-refractory mutation system, and have determined EGFR copy number by fluorescence in situ hybridization (FISH) analysis in paired tumor specimens obtained from 100 consecutive patients with advanced NSCLC treated with chemotherapy. EGFR mutations or FISH positivity (EGFR amplification or high polysomy) were apparent in 18% (18/100) and 32% (32/100) of patients, respectively. The Scorpion-amplification-refractory mutation system was more sensitive than direct sequencing for the detection of EGFR mutations. Furthermore, EGFR mutations were associated with EGFR amplification (P = 0.009) but not with FISH positivity (P = 0.266). Our results therefore suggest the existence of a significant association between EGFR mutation and EGFR amplification in patients with advanced NSCLC. (Cancer Sci 2008; 99: 2455-2460) T he epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family and has been implicated in the proliferation and survival of cancer cells. Aberrant expression of EGFR has been detected in many human epithelial malignancies, including non-small cell lung cancer (NSCLC).(1,2) This receptor has therefore been identified as a promising target for anticancer therapy, and several agents have been synthesized that inhibit its tyrosine kinase activity. EGFR tyrosine kinase inhibitors (TKI) have been evaluated most extensively in individuals with NSCLC, and they have had a substantial impact on the treatment of this disease by offering additional therapeutic options for patients with advanced NSCLC. (3)(4)(5)(6) Somatic mutations in the tyrosine kinase domain of EGFR have been detected in a subset of NSCLC patients who respond to EGFR TKI (7)(8)(9) and have been shown to be closely associated with sensitivity to these drugs.(10-14) Indeed, we and others have prospectively demonstrated a high response rate to EGFR TKI therapy in NSCLC patients with EGFR mutations. (15)(16)(17)(18)(19)(20)(21) An increased copy number of the EGFR gene, as revealed by fluorescence in situ hybridization (FISH), has also emerged as an effective molecular marker of EGFR TKI sensitivity in NSCLC. (22)(23)(24) We previously showed that EGFR mutation and EGFR amplification are associated in human NSCLC cell lines and that endogenous EGFR expressed in such cell lines positive for both of these EGFR alterations are activated constitutively.(25) However, the relationship between EGFR mutation and FI...

show abstract

“…Small (mainly East Asian) studies of egfr-tki monotherapy with gefitinib rapidly confirmed high objective response rates (55%-91%) in patients with cancers harbouring a mutation [19][20][21][22][23][24][25][26] . A large nonrandomized 217-patient Spanish-led experience 27 with erlotinib was published in 2009.…”

Section: Egfrmentioning

confidence: 89%

Biomarkers That Currently Affect Clinical Practice: EGFR, ALK, MET, KRAS

et al. 2012

View full text Add to dashboard Cite

New drugs such as pemetrexed, the epidermal growth factor receptor (egfr) tyrosine kinase inhibitors, and the Alk inhibitor crizotinib have recently enabled progress in the management of advanced non-smallcell lung cancer (nsclc). More drugs, especially Met inhibitors, will follow. However, the benefits of these agents are not uniform across the spectrum of nsclc, and optimizing their utility requires some degree of subgrouping of nsclc by the presence or absence of certain biomarkers.The biomarkers of current or imminent value are EGFR and KRAS mutational status, ALK rearrangements, and MET immunohistochemistry. As a predictor of benefit for anti-egfr monoclonal antibodies, EGFR immunohistochemistry is also of potential interest.Some of the foregoing biomarkers (EGFR, ALK, MET) are direct drivers of the malignant phenotype. As such, they are, quite rationally, the direct targets of inhibitory drugs. However, KRAS, while definitely a driver, has resisted attempts at direct pharmacologic manipulation, and its main value might lie in its role as part of an efficient testing algorithm, because KRAS mutations appear to exclude EGFR and ALK mutations. The indirect value of KRAS in determining sensitivity to other targeted agents or to pemetrexed remains controversial. The other biomarkers (EGFR, ALK, MET) may also have indirect value as predictors of sensitivity to chemotherapy in general, to pemetrexed specifically, and to radiotherapy and molecularly targeted agents.These biomarkers have all enabled the co-development of new drugs with companion diagnostics, and they illustrate the paradigm that will govern progress in oncology in the immediate future. However, in nsclc, the acquisition of sufficient biopsy material remains a stubborn obstacle to the evolution of novel targeted therapies.

show abstract

Phase II prospective study of the efficacy of gefitinib for the treatment of stage III/IV non-small cell lung cancer with EGFR mutations, irrespective of previous chemotherapy

Cited by 125 publications

References 41 publications

Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers

Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers

Association of epidermal growth factor receptor (EGFR) gene mutations with EGFR amplification in advanced non‐small cell lung cancer

Biomarkers That Currently Affect Clinical Practice: EGFR, ALK, MET, KRAS

Contact Info

Product

Resources

About