Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors vs Conventional Chemotherapy in Non–Small Cell Lung Cancer Harboring Wild-Type Epidermal Growth Factor Receptor

Lee, Jake June-Koo; Hahn, Seokyung; Kim, Dong-Wan; Suh, Koung Jin; Keam, Bhumsuk; Kim, Tae Min; Lee, Se‐Hoon; Heo, Dae Seog

doi:10.1001/jama.2014.3314

Cited by 131 publications

(87 citation statements)

References 44 publications

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“…A recent study examined 23 randomized trials of EGFR tyrosine kinase inhibitors in non-small cell lung cancer. 8 This meta-analysis of 14 570 patients found EGFR mutations sensitive to tyrosine kinase inhibitor therapy in 31% of patients (n ¼ 4473). The EGFR mutation status was predictive of progression-free survival, but the tyrosine kinase inhibitor treatment had no impact on overall survival for patients despite their EGFR mutation status.…”

Section: Lessons From Early Targeted Therapiesmentioning

confidence: 97%

Precision Medicine in Gastrointestinal Pathology

Wang

Park

2016

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure.Objective.-To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs. Data Sources.-Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs.Conclusions.-Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.

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Section: Lessons From Early Targeted Therapiesmentioning

confidence: 97%

Precision Medicine in Gastrointestinal Pathology

Wang

Park

2016

Archives of Pathology &Amp; Laboratory Medicine

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“…Patients with squamous cell carcinoma or NSCLC who do not harbor an EGFR mutation revealed a benefit from TKI compared with the best supportive care as second-line treatment (25)(26)(27)(28). However, previous meta-analyses reported that cytotoxic chemotherapy is better compared with TKI for patients without EGFR mutations (29)(30)(31).…”

Section: All Patients -----------------------------------------------mentioning

confidence: 99%

Efficacy of second‑line treatment and importance of comorbidity scores and clinical parameters affecting prognosis in elderly patients with non‑small cell lung cancer without epidermal growth factor receptor mutations

et al. 2017

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Abstract. The present study investigated the importance of comorbidity scores and clinical parameters in elderly patients with non-small cell lung cancer (NSCLC) not harboring epidermal growth factor receptor (EGFR) mutations who received second-line chemotherapy. The present study also compared the efficacy of tyrosine kinase inhibitor and cytotoxic chemotherapy as second-line treatment in elderly patients. The present study retrospectively reviewed the treatment of elderly patients with NSCLC (≥70 years old) who received second-line chemotherapy at Korea University Guro Hospital. Patients who had an EGFR mutation were excluded from the analysis. Between 2005 and 2013, 126 patients were included in the present study. The median progression-free survival (PFS) and overall survival (OS) for all patients who received second-line treatment were 2.47 months [95% confidence interval (CI), 2.08-2.86] and 8.63 months (95% CI, 5.99-11.28), respectively. A total of 52 patients (41.3%) were treated with tyrosine kinase inhibitor (TKI) and 74 (58.7%) were treated with chemotherapy. No difference was observed in the median PFS and OS between the TKI and chemotherapy groups (P=0.287 for PFS and P=0.374 for OS). The Charlson comorbidity index was not associated with survival, whereas a simplified comorbidity score and clinical factors, including poor performance status, short PFS of first-line chemotherapy, presence of brain metastasis and low serum albumin and sodium levels were significant prognostic factors in these elderly patients. Second-line chemotherapy was not beneficial to patients who had at least 3 of these factors and a median OS of 1.73 months, whereas patients who had less than 2 of these factors had a median OS of 11.50 months. For elderly lung cancer patients without EGFR mutations, clinical parameters were the most important factors affecting survival, rather than the types of drugs.

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“…For patients with advanced NSCLC that exhibit a negative or unknown EGFR mutational status or ALK rearrangements, platinum-based double chemotherapy is the typical first-line therapy (3,4). In the treatment of non-squamous cell carcinoma, pemetrexed combined with platinum demonstrates a significantly improved toxicity profile and OS, compared with taxane-or gemcitabine-based regimes (3,5,6).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum

Zhu

et al. 2016

Oncology Letters

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Abstract. Pemetrexed combined with platinum is a first-line therapy used to treat patients with advanced non-small cell lung cancer (NSCLC) that exhibit negative or unknown epidermal growth factor receptor (EGFR) mutational status or anaplastic lymphoma kinase (ALK) rearrangements. Lung adenocarcinoma (LAC) is the primary type of NSCLC. In order to prevent overtreatment, it is necessary to identify patients with LAC who may not benefit from certain chemotherapies. Patients recruited in the present study (n=129) were diagnosed with advanced LAC and received first-line pemetrexed and platinum-based chemotherapy. A microRNA (miR) microarray was used to screen the plasma miR expression profiles in a screening set of eight patients prior to and following treatment. Specifically, plasma miR-25, miR-21, miR-27b, miR-326, miR-483-5p and miR-920 were selected for reverse transcription-quantitative polymerase chain reaction analysis in a training set (n=44) prior to treatment. The screening and training set patients were all non-smokers with no prior history of serious or chronic disease. The ∆∆Cq values of these miRs were compared between the group that showed benefit from pemetrexed and platinum treatment and the group that did not. Consequently, the ∆∆Cq values of miR-25, miR-21, miR-27b and miR-326 were further determined in a validation set (n=77). The results of the present study demonstrate that plasma expression levels of miR-25, miR-21, miR-27b and miR-326, in the training and validation sets prior to treatment, were significantly different between the benefit and non-benefit groups (P≤0.001). The expression of miR-25, miR-21, miR-27b and miR-326 was upregulated in the non-benefit group and this elevation was positively correlated with decreased progression-free survival (PFS; P≤0.001). In addition, the predictive power of each miR was evaluated through receiver operating characteristic curves, in which miR-25 exhibited the highest degree of accuracy (area under the curve, 0.926; 95% confidence interval, 0.881-0.971). These results indicate that overexpression of plasma miR-25, miR-21, miR-27b and miR-326, prior to treatment, in patients with advanced LAC is predictive of non-benefit from first-line pemetrexed and platinum-based chemotherapy, and is associated with decreased PFS. Among these four miRs, miR-25 exhibited the highest degree of accuracy in predicting insensitivity, suggesting it is the most promising biomarker.

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors vs Conventional Chemotherapy in Non–Small Cell Lung Cancer Harboring Wild-Type Epidermal Growth Factor Receptor

Abstract: Among patients with advanced NSCLC harboring WT EGFR, conventional chemotherapy, compared with first-generation EGFR TKI, was associated with improvement in PFS but not overall survival.

Cited by 131 publications

References 44 publications

Precision Medicine in Gastrointestinal Pathology

Precision Medicine in Gastrointestinal Pathology

Efficacy of second‑line treatment and importance of comorbidity scores and clinical parameters affecting prognosis in elderly patients with non‑small cell lung cancer without epidermal growth factor receptor mutations

Evaluation of plasma microRNA levels to predict insensitivity of patients with advanced lung adenocarcinomas to pemetrexed and platinum

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