Non–Small Cell Lung Cancer

Ettinger, David S.; Akerley, Wallace; Borghaei, Hossein; Chang, Andrew C.; Cheney, Richard; Chirieac, Lucian R.; D’Amico, Thomas A.; Demmy, Todd L.; Ganti, Apar Kishor; Govindan, Ramaswamy; Grannis, Frederic W.; Horn, Leora; Jahan, Thierry; Jahanzeb, Mohammad; Kessinger, Anne; Komaki, Ritsuko; Kong, Feng-Ming; Kris, Mark G.; Krug, Lee M.; Lennes, Inga T.; Loo, Billy W.; Martins, Renato; O’Malley, Janis P.; Osarogiagbon, Raymond U.; Patel, Jyoti D.; Pinder-Schenck, Mary; Pisters, Katherine M.W.; Reckamp, Karen L.; Riely, Gregory J.; Rohren, Eric M.; Swanson, Scott J.; Wood, Douglas E.; Yang, Stephen C.; Hughes, Miranda; Gregory, Kristina M.

doi:10.6004/jnccn.2012.0130

Cited by 292 publications

(188 citation statements)

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“…The Oncologist [41,42]. The inferiority of EGFR-TKIs as a front-line strategy has been demonstrated in phase III trials in both unselected NSCLC [43] and patients with EGFR wild-type disease [44][45][46].…”

Section: Egfr-tki Monotherapymentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

Goss

Spaans

2016

The Oncologist

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Molecular therapies targeting epidermal growth factor receptor (EGFR) have had a profound impact on the management of advanced non-small cell lung cancer (NSCLC). EGFR inhibition with EGFR tyrosine kinase inhibitors (EGFR-TKIs) and anti-EGFR monoclonal antibodies (mAbs) in squamous NSCLC (sqNSCLC) remains controversial in patients whose tumors are not known to harbor EGFR mutations. Recent meta-analyses of EGFR-inhibition randomized trials that are adequately powered for histological subgroup analysis and anti-EGFR trials limited to patients with squamous histology afford the opportunity to revisit EGFR treatment in sqNSCLC. In unselected patients with sqNSCLC who are not eligible for chemotherapy, EGFR-TKI therapy is a valid treatment option over placebo or best supportive care, with improved progression-free survival noted in randomized controlled trials in both the first-and second-line setting and improved overall survival (OS) in the second-line setting. In patients eligible for chemotherapy, first-line combination regimens with anti-EGFR mAbs have been shown to improve OS over chemotherapy alone in patients with squamous histology in meta-analysis and more recently in the SQUIRE sqNSCLC trial (chemotherapy with and without necitumumab).In sqNSCLC patients who respond to induction chemotherapy, maintenance therapy with erlotinib delays disease progression and may improve the survival of patients with stable disease. In the second-line setting, survival outcomes are comparable between chemotherapy and EGFR-TKIs in meta-analysis, with the latter being more tolerable as a second-line therapy. Newer-generation EGFR-TKI therapies may further benefit patients with sqNSCLC who have failed first-line chemotherapy, given the positive trial results from LUX-Lung 8 (afatinib vs. erlotinib). EGFR is a valid therapeutic target in unselected/EGFR wild-type patients with squamous cell carcinoma of the lung. With the recent approval of immune checkpoint inhibitors in the second-line management of advanced sqNSCLC and their adoption as a new standard of care, there exists an opportunity for novel combination therapies to increase therapeutic efficacy and durable tumor control. As more targeted agents are approved, combination regimens that include an anti-EGFR agent should be evaluated, and the optimal sequencing of targeted therapies should be defined. The Oncologist 2016; 21:205-213Implications for Practice: Anti-epidermal growth factor receptor (EGFR) therapies remain controversial in unselected/wild-type EGFR squamous non-small cell lung cancer (NSCLC). Recent meta-analyses and squamous-only NSCLC EGFR-inhibition trials have overcome the power limitations of early trials and can now inform the management of squamous NSCLC with anti-EGFR therapies. With the approval of immunotherapeutics in the second-line management of squamous NSCLC, there exists an opportunity for novel combination therapies to improve efficacy and durable tumor control. The optimal timing and sequencing of available second-line targeted thera...

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Section: Egfr-tki Monotherapymentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

Goss

Spaans

2016

The Oncologist

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“…Although ACT is recommended for patients with tumors that have high-risk features [4,9], identifying highrisk patients still remains challenging [9,10]. Debate also exists surrounding the benefits of ACT in early-stage NSCLC and what type of ACT should be given to these patients to balance the benefits along with toxicity and cost of chemotherapy [4,[9][10][11][12][13]. Personalized medicine seeks to identify and treat patients who are most likely to achieve optimal outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…While cisplatin-based adjuvant chemotherapy (ACT) is the standard of care for patients with stage II to IIIA NSCLC [5][6][7], controversy surrounds its use in stage I disease [8]. Although ACT is recommended for patients with tumors that have high-risk features [4,9], identifying highrisk patients still remains challenging [9,10]. Debate also exists surrounding the benefits of ACT in early-stage NSCLC and what type of ACT should be given to these patients to balance the benefits along with toxicity and cost of chemotherapy [4,[9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…The minority of patients are diagnosed with early-stage disease, approximately 15% [2]; however, these patients still have a significant riskof recurrence and lung cancer death [3]. Surgical resection is recommended as the initial therapy for early-stage (stages I and II) disease [4]. While cisplatin-based adjuvant chemotherapy (ACT) is the standard of care for patients with stage II to IIIA NSCLC [5][6][7], controversy surrounds its use in stage I disease [8].…”

Section: Introductionmentioning

confidence: 99%

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Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer

et al. 2015

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Background. A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas.The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. Materials and Methods. Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and

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“…2 Oncogenic mutations not only enable tumor development but also delineate new anticancer therapy targets. 3 To date, five molecularly targeted agents have been approved for the treatment of NSCLC.…”

mentioning

confidence: 99%

KRAS driven expression signature has prognostic power superior to mutation status in non-small cell lung cancer

Nagy¹,

Santarpia²,

Gyorffy³

2017

European Journal of Cancer

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KRAS is the most frequently mutated oncogene in non-small cell lung cancer (NSCLC). However, the prognostic role of KRAS mutation status in NSCLC still remains controversial. We hypothesize that the expression changes of genes affected by KRAS mutation status will have the most prominent effect and could be used as a prognostic signature in lung cancer.We divided NSCLC patients with mutation and RNA-seq data into KRAS mutated and wild type groups. Mann-Whitney test was used to identify genes showing altered expression between these cohorts. Mean expression of the top five genes was designated as a "transcriptomic fingerprint" of the mutation. We evaluated the effect of this signature on clinical outcome in 2,437 NSCLC patients using univariate and multivariate Cox regression analysis.Mutation of KRAS was most common in adenocarcinoma. Mutation status and KRAS expression were not correlated to prognosis. The transcriptomic fingerprint of KRAS include FOXRED2, KRAS, TOP1, PEX3 and ABL2. The KRAS signature had a high prognostic power. Similar results were achieved when using the second and third set of strongest genes. Moreover, all cutoff values delivered significant prognostic power (p < 0.01). The KRAS signature also remained significant (p < 0.01) in a multivariate analysis including age, gender, smoking history and tumor stage.We generated a "surrogate signature" of KRAS mutation status in NSCLC patients by computationally linking genotype and gene expression. We show that secondary effects of a mutation can have a higher prognostic relevance than the primary genetic alteration itself.Despite advances in the last decade, lung cancer remains the most lethal tumor in women and men still exceeding the combined mortality of breast, prostate, colorectal and pancreatic cancers.1 Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancer cases and is further classified into different subtypes including adenocarcinoma (AC), squamous cell carcinoma and large cell carcinoma.

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Non–Small Cell Lung Cancer

Cited by 292 publications

References 0 publications

Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

Epidermal Growth Factor Receptor Inhibition in the Management of Squamous Cell Carcinoma of the Lung

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer

KRAS driven expression signature has prognostic power superior to mutation status in non-small cell lung cancer

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