Impact of EGFR Inhibitor in Non–Small Cell Lung Cancer on Progression-Free and Overall Survival: A Meta-Analysis

Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to influence response to targeted therapies. The principle goal of precision medicine is to define those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few "mountains" [representing the most commonly mutated genes like KRAS, epidermal growth factor (EGFR), and anaplastic lymphoma kinase (ALK)] and a vast number of "hills" (representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected.

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“…Among patients progressing to first generation EGFR TKIs, 50% have tumors with a secondary T790M mutation 15 . 16 .…”

Section: Systemic Treatment In Egfr-alk Nsclc Patients: Second Line Tmentioning

confidence: 99%

Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond

Karachaliou

Rosell

Morales-Espinosa

et al. 2014

Expert Review of Anticancer Therapy

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“…Despite modern chemotherapy and/or novel agents targeting genetic mutations and rearrangements,3, 4 the majority of advanced disease patients does not attain disease control, with 5‐year survival rates not exceeding 1–2% 3, 4, 5. Major treatment goals are therefore to minimize the patients' symptom burden and maintain functioning and quality of life (QoL) 6, 7.…”

Section: Introductionmentioning

confidence: 99%

Muscle mass and association to quality of life in non‐small cell lung cancer patients

Bye

Sjøblom

Wentzel‐Larsen

et al. 2017

J cachexia sarcopenia muscle

116

137

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BackgroundCancer wasting is characterized by muscle loss and may contribute to fatigue and poor quality of life (QoL). Our aim was to investigate associations between skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) and selected QoL outcomes in advanced non‐small cell lung cancer (NSCLC) at diagnosis.MethodsBaseline data from patients with stage IIIB/IV NSCLC and performance status 0–2 enrolled in three randomized trials of first‐line chemotherapy (n = 1305) were analysed. Associations between SMI (cm2/m2) and SMD (Hounsfield units) based on computed tomography‐images at the third lumbar level and self‐reported physical function (PF), role function (RF), global QoL, fatigue, and dyspnoea were investigated by linear regression using flexible non‐linear modelling.ResultsComplete data were available for 734 patients, mean age 65 years. Mean SMI was 47.7 cm2/m2 in men (n = 420) and 39.6 cm2/m2 in women (n = 314). Low SMI values were non‐linearly associated with low PF and RF (men P = 0.016/0.020, women P = 0.004/0.012) and with low global QoL (P = 0.001) in men. Low SMI was significantly associated with high fatigue (P = 0.002) and more pain (P = 0.015), in both genders, but not with dyspnoea. All regression analyses showed poorer physical outcomes below an SMI breakpoint of about 42–45 cm2/m2 for men and 37–40 cm2/m2 for women. In both genders, poor PF and more dyspnoea were significantly associated with low SMD.ConclusionsLow muscle mass in NSCLC negatively affects the patients' PF, RF, and global QoL, possibly more so in men than in women. However, muscle mass must be below a threshold value before this effect can be detected.

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“…The discovery of driver mutations in the epidermal growth factor receptor (EGFR) gene in a subset of patients with NSCLC and the development of oral tyrosine kinase inhibitors (TKIs) targeting these mutant receptors has remarkably changed the therapeutic landscape in advanced NSCLC. It has led to improved progression free survival as well as quality of life in this patient population (4). The prevalence of sensitizing EGFR mutation ranges from 14% to 38% in patients with NSCLC depending on geographic location and ethnicity (3).…”

Section: Introductionmentioning

confidence: 99%

Circulating DNA in EGFR-mutated lung cancer

Singh¹,

Li²,

Cheng³

2017

Ann. Transl. Med.

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Circulating tumor DNA (ctDNA) consists of short double stranded DNA fragments that are released by tumors including non-small cell lung cancer (NSCLC). With the identification of driver mutations in the epidermal growth factor receptor (EGFR) gene and development of targeted tyrosine kinase inhibitors (TKIs), the clinical outcome of NSCLC patients in this subgroup has improved tremendously.The gold standard to assess EGFR mutation is through tissue biopsy, which can be limited by difficulty in accessing the tumor, inability of patients to tolerate invasive procedures, insufficient sample for molecular testing and inability to capture intratumoral heterogeneity. The great need for rapid and accurate identification of activating EGFR mutations in NSCLC patients paves the road for ctDNA technology.Studies have demonstrated ctDNA to be a reliable complement to tumor genotyping. Platforms like digital polymerase chain reaction (PCR) and next-generation sequencing based analyses have made it possible to identify EGFR mutations in plasma with high sensitivity and specificity. This article will provide an overview on ctDNA in the context of EGFR mutated NSCLC, especially its emerging applications in diagnosis, disease surveillance, treatment monitoring and detection of resistance mechanisms.

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Impact of EGFR Inhibitor in Non–Small Cell Lung Cancer on Progression-Free and Overall Survival: A Meta-Analysis

Cited by 451 publications

References 56 publications

Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond

Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond

Muscle mass and association to quality of life in non‐small cell lung cancer patients

Circulating DNA in EGFR-mutated lung cancer

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