Journal List > J Lung Cancer > v.8(2) > 1050707

Hirsh: Comparison of Gefitinib versus Docetaxel in Patients with Pre-Treated Non-Small Cell Lung Cancer (NSCLC)


More effective treatments in first, second, and third-line of metastatic non-small cell lung cancer (NSCLC) enable patients to live longer, with a better quality of life (QOL). Especially epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) contributed to this improvement. Gefitinib was compared with Docetaxel in four randomized trials, i.e., SIGN, Japanese V-1532, Korean ISTANA, and INTEREST in second or third-line treatment of metastatic NSCLC. In all the trials, and also by meta-analysis of 2,257 patients in these trials, Gefitinib was found non-inferior or superior to Docetaxel, with less toxicity, convenient oral administration, and better QOL. Detailed results are presented in the review article. Knowing that every line of treatment we may lose about 50% of patients for further treatment, it is very important to offer each patient the best option for every line of treatment. Gefitinib has a favorable benefit-risk profile compared with Docetaxel in this patient population.


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Figures and Tables

Fig. 1.
SIGN: quality of life (QOL) & symptom improvement, LCS: lung cancer subscale, FACT-L: functional assessment of cancer therapy-lung, CI: confidence interval.
Fig. 2.
Quality of life and symptom improvement rates (EFQ population) – INTEREST. p values from logistic regression with covariates. Clinically relevant improvement pre-defined as 6-point improvement for FACT-L and TOI; 2-point improvement for LCS, maintained for at least 21 days. EFQ: evaluable for quality of life, FACT-L: functional assessment of cancer therapy-lung, TOI: trial outcome index, LCS: lung cancer subscale.
Fig. 3.
Kaplan-Meier curves of (A) overall survival and (B) progression-free survival for all patients (Meta-analysis).
Table 1.
Efficacy Data in the Second-Line Setting
Outcome Erlotinib (150 mg daily) Docetaxel (75 mg/m2 every 3 weeks) Pemetrexed (500 mg/m2 every 3 weeks)
RR, % 8.9 6.7∼8.8 9.1
Median duration of response, mo 7.9 5.3∼9.1 4.6
Median PFS, mo 2.2 2.7∼6 2.9
Median OS, mo 6.7 5.7∼7.9 8.3
1-year survival, % 31 30∼37 30
2-year survival, % 13 0 0
Median OS, mo 9.4 9.1 9.4
in PS 0/1 patients with one prior regimen      

RR: response rate, PFS: progression-free survival, OS: overall survival.

Table 2.
Demography (ITT Population) – INTEREST
  Gefitinib, % (n=733) Docetaxel, % (n=733)
Age <65 years 61 67
Female 36 33
WHO PS 0/1/2* 30/58/12 25/63/12
Never-smoker* 20 20
Second-line* 84 83
Asian origin 21 23
Adenocarcinoma* 54 55
Since diagnosis: 26/38/35 27/37/35
<6/6∼12/>12 months    
Prior platinum 54/45 56/42
Prior paclitaxel 9/9/81 8/9/82
Best response to previous 27/41/26 31/38/25
CT (CR+ PR)/SD/PD    
Locally advanced disease 14 13

WHO: world health organization, CR: complete response, PR: partial response, SD: stable disease, PD: progressive disease.

* 1 of the 6 stratification factors;

progressed during or within 3 months of completing therapy.

Table 3.
Phase III Gefitinib vs. Taxotere: Overall Survival (INTEREST)
  Gefitinib Taxotere HR (CI)
Median survival 7.6 8.0 1.02
 time, overall (n=659) (n=657) (95% CI:
 population, mo     0.905∼1.150)
Median survival 8.4 7.5 1.09
 time, high EGFR (n=85) (n=89) (95% CI:
 population, mo     0.78∼1.51)

Non-inferiority demonstrated in overall population (95% CI upper limit <1.154). Superiority NOT demonstrated in high EGFR population (p=0.6199). HR: hazard ratio, CI: confidence interval, EGFR: epidermal growth factor receptor.

Table 4.
INTEREST: Median Survival According to Clinical Factors
  Gefitinib Docetaxel
Adenocarcinomas 8.5 8.9
Other histologies 6.4 6.9
Female 11.2 10
Male 6.1 7
Never-smokers 14.1 13.9
Smokers 6.4 6.9
Asian 10.4 12.2
Non-Asian 6.9 6.9
Table 5.
INTEREST: Overall Survival According to Biomarkers
  Gefitinib Docetaxel
EGF– R+ 7.9 6.5
EGF– R– 7.5 9.2
EGF– R mutant 14.2 16.6
EGF– R wild 6.4 6
K ras mutant 7.8 4.2
K ras wild 7.5 6.3
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