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

Vera Hirsh

doi:10.6058/jlc.2009.8.2.61

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

Original Article

J Lung Cancer 2009;8(2):61-66.

Published online: 10 January 2009

DOI: https://doi.org/10.6058/jlc.2009.8.2.61

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

Vera Hirsh, M.D.

Medical Oncology Department, Royal Victoria Hospital, McGill University, Montreal, Canada

Address for correspondence Vera Hirsh, M.D. Medical Oncology Department, Room A3.04, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada Tel: 1-514-934-1934 Fax: 1-514-843-1417 E-mail: vera.hirsh@muhc.mcgill.ca

Received 20 October 2009 Accepted 1 November 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.

Keywords: Gefitinib, Docetaxel, 2nd line treatment, 3rd line treatment, Non-small cell lung carcinoma, Metastatic

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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
refractory^†/received^*
Prior paclitaxel	9/9/81	8/9/82
refractory^†/received/none^*
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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