Evaluation of epidermal growth factor receptor <i>(EGFR)</i> mutations and gene copy numbers as predictors of clinical outcomes in Japanese patients with recurrent non-small-cell lung cancer (NSCLC) receiving gefitinib

Takano, Toshimi; Ohe, Yuichiro; Yoshida, Tsuguo; Tsuta, Koji; Matsuno, Yosuke; Yamamoto, Nobuyuki; Sekine, Ikuo; Kunitoh, Hideo; Hirohashi, Shinji; Tamura, Tomohide

doi:10.1200/jco.2005.23.16_suppl.7032

Cited by 3 publications

(1 citation statement)

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“…Relationships between expression of EGFR, pMAPK, and pAkt and response to EGFR TKIs also remain to be firmly established as results have been contradictory [65][66][67][68][69][70][71][72], but there is some evidence that amplification of the EGFR gene may be linked to a higher likelihood of response and extended survival for patients with NSCLC [73,74]. Recent findings also suggest that somatic mutations in the EGFR tyrosine kinase domain may predict for good response to erlotinib and gefitinib treatment [66,73,[75][76][77][78][79], whereas K-ras mutations may be associated with poor clinical outcome for these patients [66,73].…”

Section: Erlotinibmentioning

confidence: 92%

New directions in the management of advanced pancreatic cancer: a review

Rocha-Lima¹

2008

Anti-Cancer Drugs

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Complete surgical resection is the only potentially curative option for pancreatic cancer. However, most patients have advanced/metastatic disease at the time of diagnosis, or will relapse after surgery. Systemic chemotherapy is only palliative. Gemcitabine-based therapy is an acceptable standard for unresectable locally advanced/metastatic pancreatic cancer, but average median survival is only 6 months. The addition of other chemotherapies (including other antimetabolites, platinum, and topoisomerase I inhibitors) or targeted therapies (farnesyl transferase inhibitors, metalloproteinase inhibitors, cetuximab and bevacizumab) to gemcitabine has failed to improve outcome. The combination of gemcitabine and erlotinib, a small-molecule tyrosine kinase inhibitor of the human epidermal growth factor receptor, was recently approved by the US/European authorities for use in advanced disease. In a phase III trial, the combination demonstrated a significant improvement in overall survival compared with gemcitabine monotherapy. Positive efficacy results have also been observed in a phase III trial, favoring the addition of capecitabine to gemcitabine compared with gemcitabine alone. This review focuses on the recent developments in systemic treatment, and discusses how novel agents might be incorporated into future treatment strategies for pancreatic cancer.

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Section: Erlotinibmentioning

confidence: 92%

New directions in the management of advanced pancreatic cancer: a review

Rocha-Lima¹

2008

Anti-Cancer Drugs

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Clinical Course of Patients with Non–Small Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 19 and Exon 21 Mutations Treated with Gefitinib or Erlotinib

Riely

Pao

Pham³

et al. 2006

Clinical Cancer Research

673

496

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Purpose: In patients with non^small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib.We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib. Experimental Design: In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival).Results: The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a''never smoker'' (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01). Conclusions: EGFR mutations in exons 19 or 21are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations.

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Update onEpidermal Growth Factor ReceptorMutations in Non–Small Cell Lung Cancer

Riely¹,

Politi

Miller³

et al. 2006

Clinical Cancer Research

342

265

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In 2004, several investigators reported that somatic mutations in the epidermal growth factor receptor gene were associated with clinical responses to erlotinib and gefitinib in patients with non^small cell lung cancer. Since then, multiple groups have examined the biological properties that such mutations confer as well as the clinical relevance of these mutations in patients with non^small cell lung cancer. Although a tremendous amount of knowledge has been gained in the past 2 years, there remain a number of important epidemiologic, biological, and clinical questions.

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Evaluation of epidermal growth factor receptor (EGFR) mutations and gene copy numbers as predictors of clinical outcomes in Japanese patients with recurrent non-small-cell lung cancer (NSCLC) receiving gefitinib

Cited by 3 publications

References 0 publications

New directions in the management of advanced pancreatic cancer: a review

New directions in the management of advanced pancreatic cancer: a review

Clinical Course of Patients with Non–Small Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 19 and Exon 21 Mutations Treated with Gefitinib or Erlotinib

Update onEpidermal Growth Factor ReceptorMutations in Non–Small Cell Lung Cancer

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