Predictive Factors for Interstitial Lung Disease, Antitumor Response, and Survival in Non–Small-Cell Lung Cancer Patients Treated With Gefitinib

Ando, Masahiko; Okamoto, Isamu; Yamamoto, Nobuyuki; Takeda, Koji; Tamura, Kenji; Seto, Takashi; Ariyoshi, Y; Fukuoka, Masahiro

doi:10.1200/jco.2005.04.9866

Cited by 336 publications

(236 citation statements)

References 26 publications

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“…The relatively high incidence of ILD (3.5-5.8%) in patients treated with gefitinib has been reported in Japan. It also revealed that male gender, ever-smokers, poor PS and the coincidence of interstitial pneumonia were predictive factors for the development of ILD (Yoshida, 2005;Ando et al, 2006). Although these predictive factors contrast with those for the presence of an EGFR mutation, two of the 28 patients with an EGFR mutation developed ILD in our study.…”

Section: Predictors Of Survival Benefits With Gefitinib M Satouchi Et Almentioning

confidence: 46%

“…Several subsequent retrospective studies have reported that female gender, adenocarcinoma histology, bronchioloalveolar subtype, never-smokers and patients with favourable PS are predictive factors of response Kim et al, 2005;Lim et al, 2005;Ando et al, 2006). EGFR mutation has been reported as a predictor of efficacy of gefitinib and erlotinib (Lynch et al, 2004;Pao et al, 2004).…”

Section: Predictors Of Survival Benefits With Gefitinib M Satouchi Et Almentioning

confidence: 99%

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Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

et al. 2007

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This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day À1 ) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epidermal growth factor receptor (EGFR) mutation. The lower the smoking exposure (Brinkman Index (BI) ¼ cigarettes per day Â years smoked), the better the MST (BI 0: 14.5 months, BI o500: 9.5 months, BI 500 to o1000: 6.9 months, BI X1000: 4.0 months). Positive-EGFR mutation status and PS 0 -1 were independent predictors of favourable prognosis by multivariate analysis. Prognosis was significantly different according to EGFR mutation status (with the same smoking status), but not according to smoking status (with the same EGFR mutation status). EGFR mutation status is the most important independent predictor of survival benefit with gefitinib treatment. Although differences in prognosis were observed according to relative smoking status and smoking exposure, the results suggested that smoking is not a direct predictor of prognosis, yet is a surrogate marker of EGFR mutation status.

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Section: Predictors Of Survival Benefits With Gefitinib M Satouchi Et Almentioning

confidence: 46%

Section: Predictors Of Survival Benefits With Gefitinib M Satouchi Et Almentioning

confidence: 99%

Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

et al. 2007

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“…A retrospective study of 1976 consecutive patients treated with gefitinib at 84 institutions showed that the incidence of ILD was 3.5% and the mortality rate was 1.6%. Several risk factors for the development of gefitinibinduced ILD were identified in the Japanese population: a history of pulmonary fibrosis, a history of smoking, a poor performance status, and a male sex (Ando et al, 2006). A similar incidence of ILD (4.6%) was also noted in association with erlotinib chemotherapy in Japanese phase II trials .…”

Section: Interstitial Lung Disease Associated With Gefitinib and Erlomentioning

confidence: 63%

Emerging ethnic differences in lung cancer therapy

Sekine¹,

Yamamoto²,

Nishio

et al. 2008

Br J Cancer

117

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Although global clinical trials for lung cancer can enable the development of new agents efficiently, whether the results of clinical trials performed in one population can be fully extrapolated to another population remains questionable. A comparison of phase III trials for the same drug combinations against lung cancer in different countries shows a great diversity in haematological toxicity. One possible reason for this diversity may be that different ethnic populations may have different physiological capacities for white blood cell production and maturation. In addition, polymorphisms in the promoter and coding regions of drug-metabolising enzymes (e.g., CYP3A4 and UGT1A1) or in transporters (e.g., ABCB1) may vary among different ethnic populations. For example, epidermal growth factor receptor (EGFR) inhibitors are more effective in Asian patients than in patients of other ethnicities, a characteristic that parallels the incidence of EGFR-activating mutations. Interstitial lung disease associated with the administration of gefitinib is also more common among Japanese patients than among patients of other ethnicities. Although research into these differences has just begun, these studies suggest that possible pharmacogenomic and tumour genetic differences associated with individual responses to anticancer agents should be carefully considered when conducting global clinical trials. British Journal of Cancer (2008) Lung cancer is the most common malignancy worldwide. Approximately 1.2 million people are diagnosed with lung cancer annually (accounting for 12.3% of all cancers); the second most common malignancy is breast cancer (10.4%), followed by colorectal cancer (9.4%). As lung cancer almost invariably has a poor prognosis, it is the largest single cause of death from cancer in the world, with a mortality of 1.1 million annually (Stewart and Kleihues, 2003). Only 15% of lung cancer patients have a disease that is confined to the lung and are candidates for surgical resection; most patients with this disease have distant metastases or pleural effusion at the time of their initial diagnosis. These patients can be treated with systemic chemotherapy, but the efficacy of currently available anticancer agents is limited and patients with advanced diseases rarely live long.As the development of new anticancer agents and chemotherapeutic regimens is both time and money consuming, clinical trials need to be as efficient as possible. One effort in this direction has been the adoption of global clinical trials for new agents that involve trial centres on more than one continent; this strategy enables adequate sample sizes to be obtained in a relatively short-time period and eliminates the need for redundant clinical trials with similar objectives conducted in different countries. However, whether the results of clinical trials performed in one population can be fully extrapolated to other populations remains questionable because of potential differences in trial designs, study-specific criteria, patient demographic...

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“…Interstitial lung disease is the most problematic toxicity in gefitinib treatment in Japan where an incidence of 3.5% and a fatality rate of 1.6% have been reported (Inoue et al, 2003;Ando et al, 2006). Accordingly, in the present trial, we planned to conduct biweekly chest CT for early detection of ILD during the initial treatment period.…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations

et al. 2006

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Retrospective analysis has shown that activating mutations in exons 18 -21 of the epidermal growth factor receptor (EGFR) gene are a predictor of response to gefitinib. We conducted a phase II trial to evaluate the efficacy and safety of gefitinib as first-line therapy for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Patients with stage IIIB or IV chemotherapy-naïve NSCLC with EGFR mutation were treated with 250 mg gefitinib daily. For mutational analysis, DNA was extracted from paraffin-embedded tissues and EGFR mutations were analysed by direct sequence of PCR products. Twenty (24%) of the 82 patients analysed had EGFR mutations (deletions in or near E746-A750, n ¼ 16; L858R, n ¼ 4). Sixteen patients were enrolled and treated with gefitinib. Twelve patients had objective response and response rate was 75% (95% CI, 48 -93%). After a median follow-up of 12.7 months (range, 3.1 -16.8 months), 10 patients demonstrated disease progression, with median progression-free survival of 8.9 months (95% CI, 6.7 -11.1 months). The median overall survival time has not yet been reached. Most of the toxicities were mild. This study showed that gefitinib is very active and well tolerated as first-line therapy for advanced NSCLC with EGFR mutations.

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Predictive Factors for Interstitial Lung Disease, Antitumor Response, and Survival in Non–Small-Cell Lung Cancer Patients Treated With Gefitinib

Abstract: ILD is a serious adverse effect of gefitinib in the clinical setting that cannot be ignored. However, patient selection based on sex and smoking history can minimize ILD risk and maximize the clinical benefit of gefitinib.

Cited by 336 publications

References 26 publications

Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

Predictive factors associated with prolonged survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with gefitinib

Emerging ethnic differences in lung cancer therapy

A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations

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