☆ 4.6 Review

Choosing the optimal immunotherapeutic strategies for non-small cell lung cancer based on clinical factors

FRONTIERS IN ONCOLOGY (2022)

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IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain

Naoyuki Nogami et al.

Summary: This study presents the final overall survival (OS) analyses for EGFR mutations and liver or brain metastases subgroups in the IMpower150 study. The results show that ABCP has sustained OS improvements compared to BCP in sensitizing EGFR mutations and baseline liver metastases subgroups. However, ACP does not provide a survival benefit in these subgroups compared to BCP. The study also suggests further investigation into the impact of ABCP on delaying the development of new brain lesions.

JOURNAL OF THORACIC ONCOLOGY (2022)

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Article Pathology

Heterogeneity of programmed death-ligand 1 expression and infiltrating lymphocytes in paired resected primary and metastatic non-small cell lung cancer

Jianghua Wu et al.

Summary: Metastatic tumors in non-small cell lung cancer exhibit differences in immune microenvironment compared to primary tumors, with higher PD-L1 expression levels, lower CTL density, and longer CTL-tumor cell distances. Heterogeneity in immune markers is more prominent in extrapulmonary, metachronous, and treated metastatic tumors, and correlated with EGFR mutations. Higher CD8+ CTL density in metastatic tumors is associated with better overall survival, suggesting potential implications for immunotherapy prediction in these patients.

MODERN PATHOLOGY (2022)

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Review Medicine, General & Internal

Blood Biomarkers of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

Yolanda Lage Alfranca et al.

Summary: This review summarizes the emerging blood-based markers that could help predict the response to ICIs in NSCLC, emphasizing the importance of early identification of non-responder patients to avoid unnecessary treatment and adverse events.

JOURNAL OF CLINICAL MEDICINE (2022)

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Article Oncology

Efficacy of anti-PD-1 antibodies in NSCLC patients with anEGFRmutation and high PD-L1 expression

Ken Masuda et al.

Summary: Several studies have shown that NSCLC patients with EGFR mutations have poor response to PD-1 inhibitors. However, this study found that PD-1 inhibitors can be effective in NSCLCs with EGFR mutations and high PD-L1 expression.

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY (2021)

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Article Oncology

Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer

Yoshinobu Saito et al.

Summary: This study identified poor prognostic factors of interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) treated with nivolumab, including DAD-like radiographic pattern, onset of ILD <= 60 days from nivolumab initiation, presence of pre-treatment pleural effusion, distribution of lesions contralateral or bilateral to the tumor, and abnormal changes in CRP levels. It suggests careful management for NSCLC patients developing ILD during nivolumab treatment with these poor prognostic factors.

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Article Oncology

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC

Yuki Takeyasu et al.

Summary: PD-L1 expression and absence of liver metastasis are significant predictors for a better response to pembrolizumab in patients with strongly positive PD-L1 NSCLC. Higher PD-L1 expression and lack of liver metastasis were associated with higher objective response rate and longer progression-free survival in these patients.

CLINICAL LUNG CANCER (2021)

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Review Biotechnology & Applied Microbiology

Metastatic sites as predictors in advanced NSCLC treated with PD-1 inhibitors: a systematic review and meta-analysis

Yangyun Huang et al.

Summary: This study evaluated the prognosis of advanced metastatic NSCLC patients treated with PD-1 inhibitors, finding that metastatic sites such as brain, liver, and bone can impact long-term survival outcomes. Patients with multiple metastatic sites had worse progression-free survival, while patients with brain and liver metastases were more likely to progress.

HUMAN VACCINES & IMMUNOTHERAPEUTICS (2021)

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Article Oncology

Atezolizumab Plus Chemotherapy for First-Line Treatment of Nonsquamous NSCLC: Results From the Randomized Phase 3 IMpower132 Trial

Makoto Nishio et al.

Summary: The IMpower132 study demonstrated significant improvement in PFS with APP compared to PP, but the difference in OS between the two groups was not statistically significant. APP showed favorable OS and PFS results across subgroups, with a manageable safety profile and no new or unexpected safety signals identified.

JOURNAL OF THORACIC ONCOLOGY (2021)

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Article Oncology

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

Luis Paz-Ares et al.

Summary: The combination of first-line nivolumab plus ipilimumab with a limited course of chemotherapy showed a significant improvement in overall survival for patients with advanced non-small-cell lung cancer, supporting it as a new treatment option for this patient population.

LANCET ONCOLOGY (2021)

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Article Oncology

Efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer patients with different metastases

Meng Qiao et al.

Summary: The study revealed that patients with more metastatic organs had poorer responses to immune checkpoint inhibitors, and liver metastasis was a negative predictive factor for patients treated with ICI monotherapy. Combination therapy could effectively control liver metastasis and improve treatment outcomes.

ANNALS OF TRANSLATIONAL MEDICINE (2021)

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Article Medicine, General & Internal

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial

Ahmet Sezer et al.

LANCET (2021)

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Article Medicine, General & Internal

Association of Performance Status With Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy

Kartik Sehgal et al.

Summary: This study evaluated the impact of ECOG PS score at the start of therapy on progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients treated with pembrolizumab monotherapy. Patients with ECOG PS scores of at least 2 had significantly lower disease control rates and shorter PFS and OS compared to those with ECOG PS scores of 0 or 1. Multivariable analysis confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS and OS.

JAMA NETWORK OPEN (2021)

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Editorial Material Oncology

How low can you go? PD-L1 expression as a biomarker in trials of cancer immunotherapy

A. Fundytus et al.

ANNALS OF ONCOLOGY (2021)

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Article Oncology

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189

D. Rodriguez-Abreu et al.

Summary: Pembrolizumab plus pemetrexed-platinum continues to demonstrate improved efficacy outcomes compared to placebo plus pemetrexed-platinum, with manageable toxicity, supporting its first-line use in previously untreated metastatic nonsquamous non-small-cell lung cancer patients.

ANNALS OF ONCOLOGY (2021)

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Review Pathology

An update on companion and complementary diagnostic assays for PD-1/PD-L1 checkpoint inhibitors in NSCLC

Jan Trost Jorgensen

Summary: The development in molecular medicine has deepened our understanding of malignant diseases' pathophysiology, leading to the creation of new target-specific drugs like PD-1/PD-L1 checkpoint inhibitors. PD-L1 expression assays have had a major impact on the clinical development of these inhibitors for NSCLC treatment, with studies showing efficacy positively correlated to PD-L1 expression levels. Monotherapy is recommended for NSCLC patients with high PD-L1 expression, as determined by cutoff values associated with specific PD-1/PD-L1 checkpoint inhibitors.

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Article Oncology

Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%

Martin Reck et al.

Summary: This study reports the first 5-year follow-up of a first-line immunotherapy trial for NSCLC, demonstrating that pembrolizumab provides a durable, clinically meaningful long-term overall survival benefit in first-line treatment of metastatic NSCLC with a PD-L1 tumor proportion score of at least 50%.

JOURNAL OF CLINICAL ONCOLOGY (2021)

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Review Oncology

Immune Checkpoint Inhibitors in EGFR-Mutated NSCLC: Dusk or Dawn?

Meng Qiao et al.

Summary: Although ICIs have significantly changed the treatment paradigm in advanced NSCLC, their clinical benefits are limited in patients with EGFR-mutated tumors due to the unique characteristics of the tumor microenvironment. The cancer immunogram can visualize the state of cancer-immune system interactions in EGFR-mutated NSCLC, helping identify subpopulations that may benefit from ICI treatment. Future strategies need to be developed to maximize the efficacy of ICI treatment in patients with EGFR-mutated NSCLC in the era of combination immunotherapies.

JOURNAL OF THORACIC ONCOLOGY (2021)

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Review Oncology

Strategies to overcome resistance to immune checkpoint blockade in lung cancer

Ilaria Attili et al.

Summary: Immune checkpoint inhibitors have shown impressive long-term survival results in non-small cell lung cancer, but resistance to ICI treatment is a common issue. Modulating the immune response by interfering with specific alternative immune receptors, pathways, and mediators may provide additional strategies to delay or prevent the development of resistance. Further investigation into these mechanisms aims to identify novel immune targets and evaluate potential new strategies for overcoming resistance.

LUNG CANCER (2021)

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First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update

M. Reck et al.

Summary: The updated data from the phase III CheckMate 9LA trial with a minimum 2-year follow-up show that first-line nivolumab plus ipilimumab with two cycles of chemotherapy continues to provide prolonged overall survival benefits over chemotherapy in advanced non-small-cell lung cancer patients, with manageable safety profile. Improved efficacy outcomes were observed in most subgroups with no new safety signals detected.

ESMO OPEN (2021)

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Article Biotechnology & Applied Microbiology

Anti-PD-1 Monotherapy for Advanced NSCLC Patients with Older Age or Those with Poor Performance Status

Taichi Matsubara et al.

Summary: Anti-PD-1 therapy showed comparable efficacy in older and younger patients with NSCLC, but survival was significantly worse in patients with poor performance status (PS). High PD-L1 expression in tumor specimens was associated with favorable survival outcomes.

ONCOTARGETS AND THERAPY (2021)

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Article Oncology

IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC

Mark A. Socinski et al.

Summary: The final analysis of IMpower150 study showed a numerical OS improvement with ACP compared to BCP in metastatic nonsquamous NSCLC patients, while ABCP demonstrated continued OS improvement in all patients.

JOURNAL OF THORACIC ONCOLOGY (2021)

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Article Oncology

Updated Overall Survival Analysis From IMpower110: Atezolizumab Versus Platinum-Based Chemotherapy in Treatment-Naive Programmed Death-Ligand 1-Selected NSCLC

Jacek Jassem et al.

Summary: The study demonstrated that atezolizumab did not show significant OS benefit compared to chemotherapy in NSCLC patients with lower PD-L1 expression levels, while maintaining OS benefit in patients with higher PD-L1 expression levels. Safety data continued to support the use of atezolizumab.

JOURNAL OF THORACIC ONCOLOGY (2021)

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Review Oncology

Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC

Michael J. Grant et al.

Summary: The treatment landscape of driver-negative non-small-cell lung cancer is rapidly changing due to the efficacy of immune-checkpoint inhibitors targeting PD-1 or PD-L1 as first-line therapy. Histological subtype and PD-L1 expression levels are crucial factors in regimen selection for patients, with emerging biomarkers and novel strategies potentially refining treatment paradigms in the future. Immune-checkpoint inhibitors are now standard-of-care therapies for patients with advanced-stage NSCLC, with various approved regimens available, highlighting the need for further research to optimize outcomes.

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KRAS/LKB1 and KRAS/TP53 co-mutations create divergent immune signatures in lung adenocarcinomas

Meichen Gu et al.

Summary: Lung adenocarcinomas exhibit diverse genomic alterations, with KRAS serving as a driver oncogene with high mutational frequency. Tumors with KRAS mutations may exhibit enhanced PD-L1 expression and additional somatic mutations, suggesting potential for immune checkpoint blockade therapy. Responses to this therapy vary among KRAS-mutant lung adenocarcinomas, mainly due to heterogeneity in tumoral immune milieus.

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Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis

Lei Sheng et al.

Summary: This network meta-analysis compared different first-line treatments for advanced wild-type non-small cell lung cancer patients, and showed that a combination of ICIs with chemotherapy is more effective than double ICIs in improving long-term survival.

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Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non-small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study

Hayato Kawachi et al.

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TATTON: a multi-arm, phase lb trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer

G. R. Oxnard et al.

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Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer

Shirish Gadgeel et al.

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Bevacizumab plus chemotherapy in nonsquamous non-small cell lung cancer patients with malignant pleural effusion uncontrolled by tube drainage or pleurodesis: A phase II study North East Japan Study group trial NEJ013B

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Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC

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ECOG performance status ≥2 as a prognostic factor in patients with advanced non small cell lung cancer treated with immune checkpoint inhibitors-A systematic review and meta-analysis of real world data

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Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation - Positive Advanced Non-Small Cell Lung Cancer (CheckMate 370)

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Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial

Arjun V. Balar et al.

LANCET (2017)

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Article Medicine, General & Internal

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial

Achim Rittmeyer et al.

LANCET (2017)

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Article Oncology

Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study

Matthew D. Hellmann et al.

LANCET ONCOLOGY (2017)

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Article Oncology

First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study

Arjun V. Balar et al.

LANCET ONCOLOGY (2017)

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Article Oncology

Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC

Paul C. Tumeh et al.

CANCER IMMUNOLOGY RESEARCH (2017)

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Article Respiratory System

Prognostic role of a comprehensive geriatric assessment on the management of elderly patients with advanced non-small cell lung cancer (NSCLC): a pooled analysis of two prospective phase II trials by the GFPC Group

Herve Le Caer et al.

JOURNAL OF THORACIC DISEASE (2017)

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Article Oncology

Disparities in Prostate, Lung, Breast, and Colorectal Cancer Survival and Comorbidity Status among Urban American Indians and Alaskan Natives

Marc A. Emerson et al.

CANCER RESEARCH (2017)

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Article Oncology

Hyperprogressors after Immunotherapy: Analysis of Genomic Alterations Associated with Accelerated Growth Rate

Shumei Kato et al.

CLINICAL CANCER RESEARCH (2017)

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Review Biochemistry & Molecular Biology

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy

Padmanee Sharma et al.

CELL (2017)

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Review Oncology

Role of the Microenvironment in Liver Metastasis: From Pre- to Prometastatic Niches

Pnina Brodt

CLINICAL CANCER RESEARCH (2016)

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Article Oncology

EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis

Justin F. Gainor et al.

CLINICAL CANCER RESEARCH (2016)

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Article Oncology

Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer

Naiyer A. Rizvi et al.

JOURNAL OF CLINICAL ONCOLOGY (2016)

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Article Medicine, General & Internal

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial

Louis Fehrenbacher et al.

LANCET (2016)

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Article Medicine, General & Internal

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial

Roy S. Herbst et al.

LANCET (2016)

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Article Medicine, General & Internal

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer

Martin Reck et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

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Article Oncology

Prognostic effect of liver metastasis in lung cancer patients with distant metastasis

Yijiu Ren et al.

ONCOTARGET (2016)

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Review Oncology

Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer A Systematic Review and Meta-analysis

Mizuki Nishino et al.

JAMA ONCOLOGY (2016)

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Article Radiology, Nuclear Medicine & Medical Imaging

Interstitial lung abnormalities in treatment-naive advanced non-small-cell lung cancer patients are associated with shorter survival

Mizuki Nishino et al.

EUROPEAN JOURNAL OF RADIOLOGY (2015)

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Review Oncology

Toxicities of Immunotherapy for the Practitioner

Jeffrey S. Weber et al.

JOURNAL OF CLINICAL ONCOLOGY (2015)

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Article Oncology

Upregulation of PD-L1 by EGFR Activation Mediates the Immune Escape in EGFR-Driven NSCLC Implication for Optional Immune Targeted Therapy for NSCLC Patients with EGFR Mutation

Nan Chen et al.

JOURNAL OF THORACIC ONCOLOGY (2015)

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Article Medicine, General & Internal

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer

Julie Brahmer et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

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Article Oncology

Prognostic Impact of Minimal Pleural Effusion in Non-Small-Cell Lung Cancer

Jeong-Seon Ryu et al.

JOURNAL OF CLINICAL ONCOLOGY (2014)

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Article Oncology

Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial

Yi-Long Wu et al.

LANCET ONCOLOGY (2014)

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Article Oncology

Metastatic sites and survival in lung cancer

M. Riihimaeki et al.

LUNG CANCER (2014)

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Article Oncology

VEGFA-VEGFR Pathway Blockade Inhibits Tumor-Induced Regulatory T-cell Proliferation in Colorectal Cancer

Magali Terme et al.

CANCER RESEARCH (2013)

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Article Oncology

Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations

Lecia V. Sequist et al.

JOURNAL OF CLINICAL ONCOLOGY (2013)

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Review Oncology

Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review

Marije E. Hamaker et al.

LANCET ONCOLOGY (2012)

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Article Oncology

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial

Rafael Rosell et al.

LANCET ONCOLOGY (2012)

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Article Oncology

The Risk of Cytotoxic Chemotherapy-Related Exacerbation of Interstitial Lung Disease with Lung Cancer

Hirotsugu Kenmotsu et al.

JOURNAL OF THORACIC ONCOLOGY (2011)

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Article Oncology

Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial

Tetsuya Mitsudomi et al.

LANCET ONCOLOGY (2010)

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Article Medicine, General & Internal

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

Makoto Maemondo et al.

NEW ENGLAND JOURNAL OF MEDICINE (2010)

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Article Oncology

Eligibility of patients with advanced non-small cell lung cancer for phase III chemotherapy trials

Janette Vardy et al.

BMC CANCER (2009)

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Article Medicine, General & Internal

Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer

JH Schiller et al.

NEW ENGLAND JOURNAL OF MEDICINE (2002)

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