Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial

Kim, Edward S.; Hirsh, Vera; Mok, Tony; Socinski, Mark A.; Gervais, Radj; Wu, Yi‐Long; Li, Long Yun; Watkins, Claire; Sellers, Mark; Lowe, Elizabeth S.; Sun, Yan; Liao, Mei Lin; Østerlind, Kell; Reck, Martin; Armour, Alison; Shepherd, Frances A.; Lippman, Scott M.; Douillard, Jean Yves

doi:10.1016/s0140-6736(08)61758-4

Cited by 1,113 publications

(860 citation statements)

References 26 publications

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“…In addition, once the patients are diagnosed as not harboring sensitive EGFR mutations, physicians might not treat them with EGFR-TKIs even after the relapse of first-line chemotherapy, though second-line gefitinib was previously reported to show acceptable toxicity and efficacy for patients with NSCLC harboring EGFR-sensitive mutations. 27,28 Thus, a false negative seems to be a more severe problem for patients with NSCLC harboring EGFR-sensitive mutations.…”

Section: Discussionmentioning

confidence: 99%

Direct Comparison of 3 PCR Methods in Detecting EGFR Mutations in Patients with Advanced Non–Small-Cell Lung Cancer

Ikeda

Nakamura

Yamaguchi

et al. 2012

Clinical Lung Cancer

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Micro abstractWe compared three PCR methods (mutant-enriched PCR, PNA-LNA PCR and PCR clamp) to detect EGFR mutations in 50 patients with advanced NSCLC. Seventeen were harboring EGFR mutations, five of whom showed discrepancies between the results of different PCR methods. All five responded to gefitinib, which we consider to suggest that the discrepancies were false negatives. Clinical Practice Points• Several methods have been used to detect EGFR mutations in non-small-cell lung cancer (NSCLC): however, it is not clear which is the most suitable for use in the clinic.• We compared three PCR methods (mutant-enriched PCR, PNA-LNA PCR and PCR clamp) in 50 patients with advanced NSCLC. Seventeen of the patients were harboring EGFR mutations, five of whom showed discrepancies between the results of different PCR methods. All five patients responded to gefitinib.• We considered that all of the discrepancies might be false negatives because the patients responded to gefitinib. To clarify the reasons for the false negatives of each PCR method, and establish the clinical sensitivity and specificity of each method, a large prospective clinical trial is warranted. AbstractBackground: Epidermal growth factor receptor (EGFR) mutations are predictive of

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Section: Discussionmentioning

confidence: 99%

Direct Comparison of 3 PCR Methods in Detecting EGFR Mutations in Patients with Advanced Non–Small-Cell Lung Cancer

Ikeda

Nakamura

Yamaguchi

et al. 2012

Clinical Lung Cancer

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“…However, phase III clinical trials have demonstrated that these drugs have comparable efficacy to chemotherapy in previously treated NSCLC patients, with objective response rates of only 8.9À9.1%. 1,2 There is compelling evidence that sensitivity to EGFR-TKIs correlates very strongly with the presence of somatic activating mutations in the EGFR kinase domain. 3,4 Such mutations are more frequent in patients with characteristics previously shown to correlate with clinical response to EGFR-TKIs treatment: nonsmokers, women, individuals of Asian ethnic background and those with adenocarcinoma.…”

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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“…The future of lung cancer therapy is growing brighter in light of the promising, increasingly accepted concept that biomarker discoveries can guide the selection of patients for the most appropriate treatment. For example, this concept has been applied clinically in the setting of adenocarcinoma by targeting EGFR mutations with EGFR tyrosine kinase inhibitors (7,8) and, more recently, by targeting echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocations with ALK inhibitors (9). Patients with tumors containing either of these alterations, however, constitute less than 20% of the NSCLC patient population.…”

Section: Introductionmentioning

confidence: 99%

Cotargeting Cyclin D1 Starts a New Chapter in Lung Cancer Prevention and Therapy

Kim

Lee

Wistuba

2011

Cancer Prevention Research

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Lung cancer has limited effective therapy and no effective prevention. Cytotoxic chemotherapy has not improved when combined with the epidermal growth factor receptor (EGFR) inhibitor erlotinib (standard lung cancer therapy) or with the rexinoid bexarotene. Combining erlotinib and bexarotene, however, to cotarget cyclin D1 via the retinoid X receptor and EGFR was active preclinically in KRAS-driven lung cancer cells derived from transgenic mice and in two clinical studies in lung cancer (including wild-type EGFR tumors, with or without KRAS mutations), as reported in this issue of the journal by Dragnev and colleagues (beginning on page 818). These results, along with closely related clinical results of the BATTLE program, support the promise of this cotargeting approach for lung cancer prevention and therapy and of cyclin D1 as a predictive, personalizing marker for it. Cancer Prev Res; 4(6); 779-82. Ó2011 AACR.

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Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial

Cited by 1,113 publications

References 26 publications

Direct Comparison of 3 PCR Methods in Detecting EGFR Mutations in Patients with Advanced Non–Small-Cell Lung Cancer

Direct Comparison of 3 PCR Methods in Detecting EGFR Mutations in Patients with 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

Cotargeting Cyclin D1 Starts a New Chapter in Lung Cancer Prevention and Therapy

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