Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR

Maemondo, Makoto; Inoue, Akira; Kobayashi, Kunihiko; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Harada, Masao; Yoshizawa, Hirohisa; Kinoshita, Ichiro; Fujita, Yuka; Okinaga, Shoji; Hirano, Haruto; Yoshimori, Kozo; Harada, Toshiyuki; Ogura, Takashi; Ando, Masahiro; Miyazawa, Hitoshi; Tanaka, Tomoaki; Saijo, Yasuo; Hagiwara, Koichi; Morita, Satoshi; Nukiwa, Toshihiro

doi:10.1056/nejmoa0909530

Cited by 4,887 publications

(3,731 citation statements)

References 30 publications

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“…6 Previous subgroup analysis indicated that the presence of EGFR mutation in a tumor is a strong predictor of better outcome upon gefitinib treatment, a conclusion supported by other phase III trials comparing gefitinib to platinum-doublet chemotherapy for adenocarcinoma patients selected on the basis of EGFR mutations. 7,8 Nevertheless, in the IPASS trial, EGFR mutation data were evaluated in only 437 out of 1217 patients (35.9%). Controversy has also surrounded the predictive value of the data in unselected patients, such that 10À20% of patients who had a partial response (PR) to gefitinib did not have detectable EGFR mutations.…”

Section: Introductionmentioning

confidence: 99%

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

Chung

Lee

Wang

et al. 2012

Intl Journal of Cancer

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Our study investigated whether tumor-associated macrophages (TAMs) in advanced non-small cell lung cancer (NSCLC) are related to treatment response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and may be a predictor of survival. Of 206 advanced NSCLC patients treated (first-line) with an EGFR-TKI at the study hospital from 2006 to 2009, 107 with adequate specimens for assessing CD68 immunohistochemistry as a marker of TAMs were assessed. After EGFR-TKI treatment, response was observed in 55 (51%) patients, and the median follow-up period was 13.5 months. Most TAMs were located in the tumor stroma (>95%) and positively costained with the M2 marker CD163. TAM counts were significantly higher in patients with progressive disease than in those without (p < 0.0001), a trend that remained in patients with known EGFR mutation status (n 5 59) and those with wild-type EGFR (n 5 20). High TAM counts, among other factors (e.g., wild-type EGFR), were significantly related to poor progression-free survival (PFS) and overall survival (OS) (all p < 0.0001 for TAMs). Multivariate Cox analyses showed that high TAM counts and EGFR mutations were both independent factors associated with PFS [odds ratio (OR), 8.0; 95% confidence interval (CI), 2.87-22.4; p 5 0.0001 and OR, 0.03; 95% CI, 0.003-0.31; p 5 0.003, respectively] and OS (OR, 2.641; 95% CI, 1.08-6.5; p 5 0.03 and OR, 0.14; 95% CI, 0.03-0.56; p 5 0.006, respectively). TAMs are related to treatment response irrespective of EGFR mutation and can independently predict survival in advanced NSCLC treated with an EGFR-TKI.

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Section: Introductionmentioning

confidence: 99%

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

Chung

Lee

Wang

et al. 2012

Intl Journal of Cancer

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“…5,28,29,[37][38][39] Recent studies have provided more compelling evidence of the clinical benefits of anti-EGFR treatment in the appropriate setting. 13,15,22,38,[40][41][42][43][44][45][46][47][48] Evidence from the large phase III randomized Iressa Pan-Asia Study trial and other phase III trials have prompted the American Society of Clinical Oncology to issue a provisional clinical opinion recommending the testing of EGFR mutational status in patients being considered for first line EGFR TKI therapy owing to their demonstrated benefit on progression-free survival. 22,41 Of note, they caution that no definitive benefit has been shown in patients treated with first-line TKIs in regards to overall survival.…”

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confidence: 99%

Molecular pathology of lung cancer: key to personalized medicine

et al. 2012

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The majority of lung adenocarcinoma patients with epidermal growth factor receptor-(EGFR) mutated or EML4-ALK rearrangement-positive tumors are sensitive to tyrosine kinase inhibitors. Both primary and acquired resistance in a significant number of those patients to these therapies remains a major clinical problem. The specific molecular mechanisms associated with tyrosine kinase inhibitor resistance are not fully understood. Clinicopathological observations suggest that molecular alterations involving so-called 'driver mutations' could be used as markers that aid in the selection of patients most likely to benefit from targeted therapies. In this review, we summarize recent developments involving the specific molecular mechanisms and markers that have been associated with primary and acquired resistance to EGFR-targeted therapy in lung adenocarcinomas. Understanding these mechanisms may provide new treatment avenues and improve current treatment algorithms.

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“…EGFR is activated in many malignancies, including lung cancer, and gefitinib inhibits the proliferation of cancerous cells through the inhibition of EGFR tyrosine kinase 4. Gefitinib has been reported to significantly extend the progression‐free survival period compared with conventional chemotherapy 5, 6, 7, 8. Although EGFR tyrosine kinase inhibitors, including gefitinib, have been effectively used for the treatment of lung cancer with EGFR mutations, most patients become drug resistant within a few years.…”

Section: Discussionmentioning

confidence: 99%

Lung squamous cell carcinoma with brachial soft tissue metastasis responsive to gefitinib: Report of a rare case

et al. 2016

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Metastasis of lung cancer to soft tissue is rare and patient outcomes are generally poor. There are no reports describing soft tissue metastasis in lung squamous cell carcinoma (SCC), in which gefitinib treatment was effective not only for the primary tumor but also the metastatic lesion. A 61‐year‐old Asian woman presented to our facility with pain and a mass in the brachium. An additional tumor was identified in the lung. As we suspected soft tissue metastasis of lung cancer, an incisional biopsy was performed, yielding a diagnosis of SCC. The brachial tumor continued to grow and became exposed at the biopsy site when the incisional wound dehisced. Because the biopsied specimen was positive for an epidermal growth factor receptor (EGFR) gene mutation, we commenced gefitinib administration. This treatment resulted in the rapid shrinkage of both the brachial metastasis and the primary tumor, followed by healing of the wound. Therefore, tyrosine kinase inhibitors should be used for cases that present EGFR activating mutations independently from the presence of skin and soft tissue metastases.

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Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR

Abstract: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)

Cited by 4,887 publications

References 30 publications

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

Tumor‐associated macrophages correlate with response to epidermal growth factor receptor‐tyrosine kinase inhibitors in advanced non‐small cell lung cancer

Molecular pathology of lung cancer: key to personalized medicine

Lung squamous cell carcinoma with brachial soft tissue metastasis responsive to gefitinib: Report of a rare case

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