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Abstract

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Disclosure Statement
  7. References

The efficacy of gefitinib for patients with non-adenocarcinoma non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is unclear, because only a small percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for tumors harboring EGFR mutation were non-adenocarcinoma NSCLC. A pooled analysis was conducted to clarify the efficacy of gefitinib for non-adenocarcinoma NSCLC patients harboring EGFR mutations. A systematic search of the PUBMED databases was conducted to identify all clinical reports that contained advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations and treated with gefitinib. The selected patients were advanced non-adenocarcinoma NSCLC patients harboring EGFR mutations who were treated with gefitinib and described in reports containing the data of the histology, status of EGFR mutations and response to gefitinib. This study selected 33 patients from 15 reports. Twenty-seven and three of the 33 patients were squamous cell carcinoma and adenosquamous cell carcinoma, respectively. One patient each had large-cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma. Twenty-one patients (64%) had sensitive EGFR mutations. The response rate (RR), disease control rate (DCR) and median progression-free survival (mPFS) was 27%, 67–70% and 3.0 months, respectively. These factors were statistically significantly inferior in the non-adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations selected from the same published reports (RR: 27%vs 66%, = 0.000028; DCR: 67–70%vs 92–93%, = 0.000014; mPFS: 3.0 vs 9.4 months, = 0.0001, respectively). Gefitinib is less effective in non-adenocarcinoma NSCLC harboring EGFR mutations than adenocarcinoma harboring EGFR mutations. (Cancer Sci 2011; 102: 1032–1037)

Gefitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), is used for the treatment of non-small-cell lung cancer (NSCLC). Two study groups have demonstrated the presence of EGFR mutations in some NSCLC patients and reported higher response rates (RR) to gefitinib therapy among these patients.(1,2) The deletion of exon 19 and point-mutation of exon 21 from T to G at codon 858 (L858R) are the most frequently encountered EGFR mutations, accounting for 90% of all the cases.(3) Approximately 3% of the mutations occur at codon 719 resulting in the substitution of glycine to cysteine, alanine or serine (G719X). In addition, approximately 3% are in-frame insertion mutations in exon 20.(4) The RR was the highest in patients with exon 19 deletions followed by L858R and G719X (81%, 71% and 56%, respectively).(5) In contrast, there are no reports of a single patient with the exon 20 insertion mutation who responded to EGFR-TKI.(5) Clinical trials were conducted based on these findings, which showed that gefitinib is an effective treatment option for first-line treatment in NSCLC patients harboring sensitive EGFR mutations with median progression-free survival (PFS) of 9.2–10.8 months and median overall survival time (MST) of 30.5 months.(6–8)

There are different treatment strategies and standard chemotherapeutic regimens for small-cell lung cancer (SCLC) and NSCLC. Furthermore, the introduction of bevacizumab and pemetrexed to NSCLC treatment made the treatment strategy and chemotherapeutic regimen different between the histological subtypes (e.g. adenocarcinoma, squamous cell carcinoma and large-cell carcinoma) because both the toxicity of bevacizumab and efficacy of pemetrexed differ between the histological subtypes.(9–12)

Epidermal growth factor receptor mutations can be detected in 30% of adenocarcinoma patients; however, they are detected in only 2.0% of non-adenocarcinoma NSCLC patients.(5) Epidermal growth factor receptor mutations can be detected in 27–44%, 0–1.1% and 0–11.5% of adenosquamous cell carcinoma, squamous cell carcinoma and large-cell carcinoma, respectively.(13–16) However, only a small percentage of patients enrolled in the clinical trials mentioned above had non-adenocarcinoma NSCLC, thus the efficacy of gefitinib for these patients is unclear. Therefore, a pooled analysis was conducted to extract and compile the data from the published reports and clarify the efficacy of gefitinib for non-adenocarcinoma NSCLC patients harboring EGFR mutations.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Disclosure Statement
  7. References

Literature search.  A systematic search of the PUBMED databases was conducted to identify all clinical trials and case reports that contained advanced or recurrent non-adenocarcinoma NSCLC patients who had somatic EGFR mutations and were treated with gefitinib. The search strategy included articles from April 2004 to June 2010 indexed under the subject headings EGFR, mutation and lung cancer. The search did not have any restrictions on the type of publication or periodical. Preliminary sets published as abstracts or the proceedings of meeting were not included. The study selected all published reports that contained the data of efficacy of gefitinib for advanced or recurrent non-adenocarcinoma NSCLC patients harboring EGFR mutations. The search was also restricted to manuscripts published in the English language.

Patient selection and EGFR mutation analysis.  The criteria for the selection of patients included in these published reports were: (i) those with cytologically or histologically proven advanced or recurrent non-adenocarcinoma NSCLC excluding not otherwise specified (NOS) with a somatic EGFR mutation and were treated with gefitinib; and (ii) those in reports that included the histology, status of EGFR mutation and response to gefitinib.

Mutations in the tyrosine kinase domain of EGFR were identified using the protocols as described in each study.(17–31) The study included any reports based on the method of DNA isolation from fresh tissue or paraffin-embedded tissue, and the technique used to enhance tumor-derived DNA, which included either microdissection or use of the more sensitive polymerase chain reaction (PCR) amplification techniques. Not all consecutive NSCLC patients were included in the EGFR mutation analysis in every study.

Treatment schedule, response, survival assessment and statistical analysis.  All of the identified patients took 250 mg/day gefitinib orally once a day. Although the treatment response was determined by the Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization (WHO) criteria or the European Cooperative Oncology Group (ECOG) criteria, RECIST was used in most of the studies. Response rates were calculated as the proportion of the number of patients evaluated to have either a complete response (CR) or partial response (PR) to the total number of patients. The disease control rate (DCR) was defined as the proportion of the number of patients evaluated as CR, PR, stable disease (SD) or no change (NC) to the total number of patients. Progression-free survival (PFS) was defined as the period from the start of treatment to the date when disease progression or death was observed. The PFS was censored at the date of the last visit for those patients who were alive without documented disease progression. Median PFS was calculated using the Kaplan–Meier method. The analysis used direct data extracted from the author’s publications for RR, DCR and PFS.

In addition, the study analyzed the data of the types of EGFR mutations, response and PFS in adenocarcinoma patients harboring EGFR mutations selected from the same published reports in order to compare the proportion of the sensitive EGFR mutations and the efficacy of gefitinib between non-adenocarcinoma NSCLC patients harboring EGFR mutations and adenocarcinoma patients harboring EGFR mutations.

The proportions of the patients harboring sensitive EGFR mutation, the RR and DCR were compared using the χ2 test. The PFS were compared using the log-rank test. Statistical analyses were performed using the StatView software program, Ver. 5.0 (SAS Institute Inc., Cary, NC, USA).

Results

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Disclosure Statement
  7. References

Characteristics of the selected patients.  Thirty-three patients with advanced or recurrent non-adenocarcinoma NSCLC who had the somatic EGFR mutations and were treated with gefitinib were selected from 15 reports.(17–31)Table 1 summarizes the 15 identified clinical reports. The 15 reports included five prospective studies and 10 retrospective studies including four studies using the data of expanded access programs of gefitinib. Thirteen of these reports originated from countries in East Asia.

Table 1.   Characteristics taken from the published reports from which we could extract the data of advanced or recurrent non-adenocarcinoma NSCLC patients who had the somatic EGFR mutation and were treated with gefitinib
AuthorYear publishedStudy designCountry of originNo. NSCLC patientsNo. non-adenocarcinoma NSCLC patients
Harboring EGFR mutationHarboring EGFR mutation
  1. †All patients included in the study had pleomorphic carcinoma of the lung. ‡All patients included in the study had squamous cell carcinoma of the lung. EAP, expanded access program; EGFR, epidermal growth factor receptor; NSCLC, non-small-cell lung cancer.

Chou et al.(17)2005Prospective single arm phase II trialTaiwan334
Han et al.(18)2005Prospective single arm phase II trialKorea171
Asahina et al.(19)2006Prospective single arm phase II trialJapan211
D’Addario et al.(20)2008Prospective single arm phase II trialSwitzerland41
Tamura et al.(21)2008Prospective single arm phase II trialJapan321
Kim et al.(22)2005Retrospective trial using the data of EAPKorea82
Zhang et al.(23)2005Retrospective trial using the data of EAPChina121
Pallis et al.(24)2007Retrospective trial using the data of EAPGreece258
Xu et al.(25)2009Retrospective trial using the data of EAPChina324
Mu et al.(26)2005Retrospective trialChina122
Tokumo et al.(27)2005Retrospective trialJapan91
Ichihara et al.(28)2007Retrospective trialJapan383
Kimura et al.(29)2007Retrospective trialJapan101
Kaira et al.(30)2009Retrospective trialJapan1†1†
Park et al.(31)2009Retrospective trialKorea3‡3‡

Table 2 shows the individual patients’ data of the non-adenocarcinoma NSCLC patients harboring EGFR mutations extracted from the published reports. In addition, Table 3 shows the subset data of non-adenocarcinoma NSCLC patients harboring EGFR mutations extracted from the published reports. Twenty-seven patients and three patients had squamous cell carcinoma and adenosquamous cell carcinoma, respectively. Large-cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma occurred in one patient each. Twenty-one patients (64%) had sensitive EGFR mutations, defined as exon 19 deletion, G719X, L858R or L861Q of EGFR. One patient had both a sensitive mutation (L858R) and resistant mutation (T790M). On the other hand, 167 patients (84%) had sensitive EGFR mutations among 199 adenocarcinoma patients harboring EGFR mutations selected from the same published reports. The difference between non-adenocarcinoma NSCLC and adenocarcinoma in the proportion of patients harboring sensitive EGFR mutations to the patients harboring any EGFR mutations was statistically significant in the χ2 test (= 0.0059). Definitive data of age, sex, performance status (PS) and smoking history could be extracted in 14 (42%), 32 (97%), six (18%) and 25 (76%) of the 33 patients, respectively. The median age was 63 years, ranging from 29 to 80. Sex, PS and smoking history were: male (21/32, 66%), female (11/32, 34%); PS 0–2 (10/12, 83%), PS 3 (2/12, 17%); smoker (15/25, 60%), never smoker (10/25, 40%).

Table 2.   Individual patient data of the non-adenocarcinoma NSCLC patients with EGFR mutations extracted from the studies that evaluated the efficacy of gefitinib for NSCLC patients with EGFR mutations
AuthorHistologyType of mutationAge (years)SexPSSmokingLineResponsePFS (months)OS (months)
  1. AS, adenosquamous cell carcinoma; CR, complete response; EGFR, epidermal growth factor receptor; La, large-cell carcinoma; NSCLC, non-small-cell lung cancer; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; PS, performance status; SD, stable disease; Sq, squamous cell carcinoma.

Chou et al.(17)SqExon 19 del56M2Never3SD2.42.5
SqExon 20 A763V80F3Never1PD1.91.9
SqExon 21 N826S57M1Former2SD6.79
SqExon 21 L858R29M3Current3PD22.5
Han et al.(18)SqExon 21 A859TFPD25.0+
Asahina et al.(19)SqExon 19 del63F0–2Former1PD0.56.9
D’Addaro et al.(20)SqExon 21 L858R0–11SD/PD
Tamura et al.(21)SqExon 19 del, Exon 21 L858R or Exon 21 L861QF0–2Never1–3CR/PR
Kim et al.(22)SqExon 19 del54FNever1–4PR
Zhang et al.(23)SqExon 19 delMNever≥2SD3.14.6
Pallis et al.(24)SqExon 19 delMNever≥2SD
SqExon 18 Y727HMCurrent≥2SD
SqExon 21 V843IMFormer≥2SD
SqExon 21 K860EMCurrent≥2PD
SqExon 18 L692PMCurrent≥2PD
SqExon 21 L858R + Exon 18 E709KFNever≥2PR3
SqExon 19 delMNever≥2SD
SqExon 18 E711KMCurrent≥2PD
Xu et al.(25)SqExon 18 A702SF0–3Never≥2PR8.514.0+
SqExon 18 G721AF0–3Never≥2CR711.0+
SqExon 19 delM0–3Yes≥2SD11.0+11.0+
ASExon 21 L858RM0–3Yes≥2PR5.3+5.3+
Mu et al.(26)SqExon 19 del63MSD
SqExon 20 Q787Q70MPD
Tokumo et al.(27)ASExon 21 L858R77F12SD
Ichihara et al.(28)SqExon 19 G719SMSD6.310.8
SpindleExon 18 G721DMPD0.78
ASExon 21 L858R + Exon 20 T790MFSD1.68.7
Kimura et al.(29)LaExon 19 del59MCurrent1–3PD
Kaira et al.(30)PleomorphicExon 21 L858R72F0Yes2SD310.5
Table 3.   Subset data of the non-adenocarcinoma NSCLC patients with EGFR mutations extracted from the study that evaluated the efficacy of gefitinib for NSCLC patients with EGFR mutations
AuthorHistologyType of mutationAge (years)SexPSSmokingLineResponsemPFS (months)MST (months)
  1. CR, complete response; EGFR, epidermal growth factor receptor; mPFS, median progression free survival; MST, median survival time; NSCLC, non-small-cell lung cancer; PR, partial response; PS, performance status; pt, patient; Sq, squamous cell carcinoma.

Park et al.(31)Sq in 3 ptsExon 19 del in 2 pts Exon 21 L858R in 1 pt63 (median) 42–69 (range)M0–21 current smoker 2 former smokers2 or 33 CR/PR5.89.6

Response to gefitinib in non-adenocarcinoma NSCLC patients harboring EGFR mutation.  A response to gefitinib was observed in 27% of non-adenocarcinoma NSCLC patients harboring EGFR mutations (Table 4). Eight (30%) of the 27 squamous cell carcinoma patients responded to gefitinib. One patient responded to gefitinib among the three adenosquamous cell carcinoma patients, and no patients with large-cell carcinoma, pleomorphic carcinoma and spindle cell carcinoma responded to gefitinib. On the other hand, 66% of the 199 adenocarcinoma patients harboring EGFR mutations, selected from the same published reports, responded to gefitinib. The difference of the RR between non-adenocarcinoma NSCLC and adenocarcinoma was statistically significant (χ2 test; = 0.000028).

Table 4.   Response rate, disease control rate and median progression-free survival according to the histology in patients harboring EGFR mutations
 Response rate (%)Disease control rate (%)mPFS (months)
  1. †The data of PFS could be extracted in 19 patients. ‡The data of PFS could be extracted in 133 patients. EGFR, epidermal growth factor receptor; mPFS, median progression-free survival; NSCLC, non-small-cell lung cancer.

Non-adenocarcinoma NSCLC (= 33)2767–703.0 (= 19†)
 Squamous cell carcinoma (= 27)3067–703.1 (= 15)
 Adenosquamous cell carcinoma (= 3)331001.6/5.3+ (= 2)
 Large-cell carcinoma (= 1)00
 Pleomorphic carcinoma (= 1)01003.0 (= 1)
 Spindle cell carcinoma (= 1)000.7 (= 1)
Adenocarcinoma (= 199)6692–939.4 (n = 133‡)

The DCR was 67–70% in non-adenocarcinoma NSCLC patients harboring EGFR mutations (Table 4). The DCR was also 67–70% in the 27 squamous cell carcinoma patients. All of the three adenosquamous cell carcinoma patients responded or showed SD/NC, and one pleomorphic carcinoma patient showed SD/NC. One large-cell carcinoma patient and one spindle cell carcinoma patient showed PD. On the other hand, the DCR was 92–93% in the 199 adenocarcinoma patients harboring EGFR mutations. The difference of the DCR between non-adenocarcinoma NSCLC and adenocarcinoma was statistically significant (χ2 test; = 0.000014).

Even if the patients to be analyzed were limited to those harboring “sensitive” EGFR mutations, the differences in the RR and the DCR between non-adenocarcinoma NSCLC and adenocarcinoma were almost the same (Table 5). The difference in the RR between non-adenocarcinoma NSCLC and adenocarcinoma harboring sensitive EGFR mutations was statistically significant (35%vs 69%, χ2 test; P = 0.000013). In addition, the difference in the DCR between non-adenocarcinoma NSCLC and adenocarcinoma harboring sensitive EGFR mutation was also statistically significant (80%vs 94–95%, χ2 test; = 0.024).

Table 5.   Response rate, disease control rate and median progression-free survival according to the histology in patients harboring sensitive EGFR mutations
 Response rate (%)Disease control rate (%)mPFS (months)
  1. Sensitive mutation was defined as exon 19 deletion, G719X, L858R or L861Q of EGFR. †One patient who had L858R and T790M was excluded. ‡The data of PFS could be extracted in 12 patients. §The data of PFS could be extracted in 109 patients. EGFR, epidermal growth factor receptor; mPFS, median progression-free survival; NSCLC, non-small-cell lung cancer.

Non-adenocarcinoma NSCLC (= 20†)35803.1 (= 12‡)
 Squamous cell carcinoma (= 16)3881–883.1 (= 10)
 Adenosquamous cell carcinoma (= 2)501005.3+ (= 1)
 Large-cell carcinoma (= 1)00
 Pleomorphic carcinoma (= 1)01003.0 (= 1)
Adenocarcinoma (= 167)6994–959.8 (= 109§)

Progression-free survival of non-adenocarcinoma NSCLC patients with an EGFR mutation treated with gefitinib.  Progression-free survival was identified in the 19 non-adenocarcinoma NSCLC patients harboring EGFR mutations (Table 4). The median PFS of non-adenocarcinoma NSCLC patients harboring EGFR mutations was 3.0 months. The median PFS in the 15 squamous cell carcinoma patients was 3.1 months. The PFS of the two adenosquamous cell carcinoma patients was 1.6 and 5.3 months. The patient with a PFS of 5.3 months was censored. The PFS of the pleomorphic carcinoma patient and the spindle cell carcinoma patient was 3.0 and 0.7 months. The PFS in the non-adenocarcinoma NSCLC patients harboring EGFR mutations was statistically inferior to adenocarcinoma patients harboring EGFR mutations (median: 3.0 vs 9.4 months, = 0.0001; Fig. 1, Table 4).

image

Figure 1.  Kaplan–Meier curves for progression-free survival (PFS) comparing non-adenocarcinoma non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations with adenocarcinoma patients harboring EGFR mutations. The PFS in the non-adenocarcinoma NSCLC patients harboring EGFR mutations was statistically inferior to adenocarcinoma patients harboring EGFR mutations (median: 3.0 vs 9.4 months, = 0.0001).

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Progression-free survival was identified in the 12 non-adenocarcinoma NSCLC patients harboring sensitive EGFR mutations (Table 5). The median PFS of non-adenocarcinoma NSCLC patients harboring sensitive EGFR mutations was 3.1 months. The median PFS was 3.1 months in the 10 squamous cell carcinoma patients. The median PFS of one adenosquamous cell carcinoma patient and one pleomorphic carcinoma patient was 5.3 and 3.0 months, respectively. The patient with a PFS of 5.3 months was censored. The PFS in non-adenocarcinoma NSCLC patients harboring sensitive EGFR mutations was statistically inferior to adenocarcinoma patients harboring sensitive EGFR mutations (median: 3.1 vs 9.8 months, = 0.0018; Fig. 2, Table 5).

image

Figure 2.  Kaplan–Meier curves for progression-free survival (PFS) comparing non-adenocarcinoma non-small-cell lung cancer (NSCLC) patients harboring sensitive epidermal growth factor receptor (EGFR) mutations with adenocarcinoma patients harboring sensitive EGFR mutations. The PFS in non-adenocarcinoma NSCLC patients harboring sensitive EGFR mutations was statistically inferior to adenocarcinoma patients harboring sensitive EGFR mutations (median: 3.1 vs 9.8 months, = 0.0018). Sensitive mutation was defined as exon 19 deletion, G719X, L858R or L861Q of EGFR.

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Discussion

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Disclosure Statement
  7. References

Gefitinib is one of the key drugs for the treatment of NSCLC patients harboring EGFR mutations. However, only a small percentage of patients enrolled in the clinical trials to evaluate the efficacy of gefitinib for NSCLC harboring EGFR mutation were non-adenocarcinoma NSCLC, and therefore the efficacy of gefitinib for these patients is unclear. This is the first report that focused on and investigated the efficacy of gefitinib for non-adenocarcinoma NSCLC patients harboring EGFR mutations.

This pooled analysis demonstrated that the RR, DCR and PFS were significantly inferior in non-adenocarcinoma NSCLC patients harboring EGFR mutations to adenocarcinoma patients harboring EGFR mutations. Yamane et al. reported that the proportion of non-adenocarcinoma patients was statistically higher in patients harboring EGFR mutations other than the exon 19 deletions and exon 21 L858R than in patients harboring EGFR mutations of exon 19 deletions or exon 21 L858R. In addition, the patients harboring only EGFR mutations other than exon 19 deletion and exon 21 L858R did not respond to gefitinib.(32) This is consistent with the findings of the current study that found that the proportion of patients harboring sensitive EGFR mutations to the patients harboring any EGFR mutations was significantly higher in adenocarcinoma patients than in non-adenocarcinoma NSCLC patients. However, there were statistically significant differences in the RR, DCR and PFS between non-adenocarcinoma NSCLC patients and adenocarcinoma patients, even though the patients who did not have sensitive EGFR mutations were excluded from the analysis.

The PI3K (phosphatidylinositol 3-kinases)/Akt pathway lies downstream of the EGFR. Alterations (mutation and copy number gain) in PIK3CA, encoding a subunit of PI3K, were associated with increased PI3K activity and increased expression of phosphorylated Akt.(33) Cetuximab, a monoclonal antibody to the EGFR, plus chemotherapy was less effective in metastatic colorectal cancer patients harboring PIK3CA mutations than those with wild-type PI3CA.(34) PIK3CA mutation and copy number gains were more frequent in squamous cell carcinoma of the lung than in adenocarcinoma.(33,35,36) In addition, the mutational status of PIK3CA was not mutually exclusive to EGFR.(33,37) Based on these findings, some genetic alterations downstream of the EGFR may cause resistance to EGFR-TKI in non-adenocarcinoma NSCLC patients harboring EGFR mutations.

Because the inherent histological heterogeneity exists in NSCLC and the morphological features of squamous or adenocarcinoma differentiation are focal or not distinguishable in small biopsy or cytology specimens, 10% of squamous cell carcinomas, 14% of adenocarcinomas and 50% of large-cell carcinomas were misclassified on the bronchial biopsies.(38) Although it cannot be denied that some of the non-adenocarcinoma NSCLC patients selected in this analysis were actually adenocarcinoma patients, gefitinib might be less effective for NSCLC with a non-adenocarcinoma morphological feature harboring EGFR mutations.

Two clinical reports contain data of the efficacy of erlotinib for advanced or recurrent non-adenocarcinoma NSCLC patients harboring EGFR mutations. These two reports were prospective phase II trials. Jackman et al.. reported that a 73-year-old male squamous cell carcinoma patient with the exon 21 L858R received erlotinib and showed SD.(39) The patient’s PFS from the initiation of erlotinib was 3.4 months. Rosell et al. reported 19 large-cell carcinoma patients harboring exon 19 deletions or exon 21 L858R EGFR mutations received erlotinib, and the hazard ratio of the PFS was 1.15 in comparison with 176 adenocarcinoma patients harboring the exon 19 deletion or exon 21 L858R EGFR mutations.(16) These findings suggest that erlotinib might be more effective for non-adenocarcinoma NSCLC, especially large-cell carcinoma, patients harboring EGFR mutations than gefitinib.

The limitations of this study must be addressed. The inclusion criteria were different among the individual studies. Moreover, the detailed patients’ characteristics could not be completely extracted in all of the 33 non-adenocarcinoma NSCLC patients and the 199 adenocarcinoma patients with EGFR mutations. Therefore, this study has a bias against the effectiveness of gefitinib. Further prospective or retrospective multicenter studies with large sample sizes are warranted. However, this compilation of patients in the published reports contains useful data, because the frequency of EGFR mutations is rare in non-adenocarcinoma NSCLC patients.

In conclusion, gefitinib might be a less effective treatment option for non-adenocarcinoma NSCLC patients harboring EGFR mutations because the RR, DCR and PFS in non-adenocarcinoma NSCLC patients harboring EGFR mutations were significantly inferior to adenocarcinoma patients harboring EGFR mutations. Moreover, because the frequency of EGFR mutations is rare in non-adenocarcinoma NSCLC patients, the value of analyzing EGFR mutations as a predictive factor is therefore considered to be limited in these patients.

Disclosure Statement

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Disclosure Statement
  7. References

None of the authors have any financial or personal relationships that could influence their work.

References

  1. Top of page
  2. Abstract
  3. Patients and Methods
  4. Results
  5. Discussion
  6. Disclosure Statement
  7. References
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