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Personalized maintenance therapy in advanced non-small cell lung cancer.

ABSTRACT: Maintenance therapy is a treatment strategy that can prolong survival in patients with advanced non-small cell lung cancer (NSCLC). The increased survival achieved with maintenance therapy has led to new treatment options that should be chosen in accordance with the preferences of patients and physicians. Personalized maintenance therapy involves identification of histological subtypes and molecular features of tumors, thereby improving treatment outcomes. Many clinical trials have been conducted to establish new treatment strategies for patients with advanced NSCLC with non-squamous cell histology. The discovery of epidermal growth factor receptor (EGFR) mutations was the most significant innovation for personalized therapy in NSCLC patients. First generation EGFR-tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have significantly contributed to greatly increased survival in specific patients harboring activating EGFR mutations such as exon 19 deletion and L858R point mutation. Based on clinical trials of different maintenance therapy strategies, we identified the regimen is the most promising and highlighted for patients whom should be given specific kinds of therapy now and in future studies.

SUBMITTER: Asami K

PROVIDER: S-EPMC4367627 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Personalized maintenance therapy in advanced non-small cell lung cancer.

Asami Kazuhiro K Okishio Kyoichi K Kawaguchi Tomoya T Atagi Shinji S

Translational lung cancer research 20131201 6

Maintenance therapy is a treatment strategy that can prolong survival in patients with advanced non-small cell lung cancer (NSCLC). The increased survival achieved with maintenance therapy has led to new treatment options that should be chosen in accordance with the preferences of patients and physicians. Personalized maintenance therapy involves identification of histological subtypes and molecular features of tumors, thereby improving treatment outcomes. Many clinical trials have been conducte ...[more]

PMID: 25806269

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Project description:IntroductionAdvanced non-small cell lung cancer (NSCLC) is a severe disease with burdensome symptoms and traditionally poor outcomes. The treatment of advance disease is based on chemotherapy, with the recent addition of immunotherapy. Patients who respond to initial treatment can opt to receive maintenance therapy (MT). It is important to understand why patients with advanced NSCLC choose to accept or refuse therapy, and how physician recommendations play into this decision-making process. This study characterized patient and physician decision-making regarding treatment for patients with advanced non-squamous NSCLC in the USA using the example of MT.Methods and materialsThis study employed multiple approaches: patient interviews, a patient survey, and a physician survey. Qualitative interviews were conducted among patients who had been offered MT to identify factors influencing treatment decision-making. The patient survey explored the decision-making process and quantified challenges and motivators for receiving MT. The physician survey included a discrete choice experiment to understand the relationship between physician treatment recommendations and patient characteristics.ResultsInterviewed patients (n = 10) were motivated to receive MT in the hope of extending their lives and being proactive against their cancer, and they anticipated reduced adverse effects compared with first-line therapy. Surveyed patients (n = 77) described several deterrents to receiving therapy; the most prominent was severity of adverse effects, which was an influencing factor for 34% of patients. The major motivator for receiving therapy was the potential to extend life, which influenced 97% of patients. A total of 100 oncologists participated in the physician survey. Patients' lack of treatment motivation/inconvenience, disease progression, presence of severe renal co-morbidities, and older age decreased the likelihood of physicians recommending the use of MT.ConclusionThis study identified challenges and motivators influencing advanced NSCLC patients' decisions to accept or refuse therapy, as well as patient and disease characteristics associated with physician's treatment recommendations for MT.

Project description:BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), gefitinib and erlotinib have been tested as maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC). The studies are quite heterogenous regarding study size and populations, and a synopsis of these data could give some more insight in the role of maintenance therapy with TKI.MethodsIn September 2012 we performed a search in the pubmed, EMBASE and Cochrane library databases for randomized phase III trials exploring the role of gefitinib or erlotinib in advanced non-small cell lung cancer. Through a rigorous selection process with specific criteria, five trials (n = 2436 patients) were included for analysis. Standard statistical methods for meta-analysis were applied.ResultsTKIs (gefitinib and erlotinib) significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.50-0.76, I(2) = 78.1%] and overall survival (HR 0.84, 95% CI 0.76-0.93, I(2) = 0.0%) compared with placebo or observation. The PFS benefit was consistent in all subgroups including stage, sex, ethnicity, performance status, smoking status, histology, EGFR mutation status, and previous response to chemotherapy. Patients with clinical features such as female, never smoker, adenocarcinoma, Asian ethnicity and EGFR mutation positive had more pronounced PFS benefit. Overall survival benefit was observed in patients with clinical features such as female, non-smoker, smoker, adenocarcinoma, and previous stable to induction chemotherapy. Severe adverse events were not frequent. Main limitations of this analysis are that it is not based on individual patient data, and not all studies provided detailed subgroups analysis.ConclusionsThe results show that maintenance therapy with erlotinib or gefitinib produces a significant PFS and OS benefit for unselected patients with advanced NSCLC compared with placebo or observation. Given the less toxicity of TKIs than chemotherapy and simple oral administration, this treatment strategy seems to be of important clinical value.

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Personalized maintenance therapy in advanced non-small cell lung cancer.

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Personalized maintenance therapy in advanced non-small cell lung cancer.

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