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How close are we to customizing chemotherapy in early non-small cell lung cancer?

ABSTRACT: Although surgery is the only potentially curative treatment for early-stage non-small cell lung cancer (NSCLC), 5-year survival rates range from 77% for stage IA tumors to 23% in stage IIIA disease. Adjuvant chemotherapy has recently been established as a standard of care for resected stage II-III NSCLC, on the basis of large-scale clinical trials employing third-generation platinum-based regimens. As the overall absolute 5-year survival benefit from this approach does not exceed 5% and potential long-term complications are an issue of concern, the aim of customized adjuvant systemic treatment is to optimize the toxicity/benefit ratio, so that low-risk individuals are spared from unnecessary intervention, while avoiding undertreatment of high-risk patients, including those with stage I disease. Therefore, the application of reliable prognostic and predictive biomarkers would enable to identify appropriate patients for the most effective treatment.This is an overview of the data available on the most promising clinicopathological and molecular biomarkers that could affect adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine practice. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information warranting further validation. On the other hand, real-time quantitative polymerase-chain reaction strategy involving relatively small number of genes offers a practical alternative, with high cross-platform performance. Although data extrapolation from the metastatic setting should be cautious, the concept of personalized, pharmacogenomics-guided chemotherapy for early NSCLC seems feasible, and is currently being evaluated in randomized phase 2 and 3 trials. The mRNA and/or protein expression levels of excision repair cross-complementation group 1, ribonucleotide reductase M1 and breast cancer susceptibility gene 1 are among the most potential biomarkers for early disease, with stage-independent prognostic and predictive values, the clinical utility of which is being validated prospectively. Inter-assay discordance in determining the biomarker status and association with clinical outcomes is noteworthing.

SUBMITTER: Ioannidis G

PROVIDER: S-EPMC3150068 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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How close are we to customizing chemotherapy in early non-small cell lung cancer?

Ioannidis Georgios G Georgoulias Vassilis V Souglakos John J

Therapeutic advances in medical oncology 20110701 4

Although surgery is the only potentially curative treatment for early-stage non-small cell lung cancer (NSCLC), 5-year survival rates range from 77% for stage IA tumors to 23% in stage IIIA disease. Adjuvant chemotherapy has recently been established as a standard of care for resected stage II-III NSCLC, on the basis of large-scale clinical trials employing third-generation platinum-based regimens. As the overall absolute 5-year survival benefit from this approach does not exceed 5% and potentia ...[more]

PMID: 21904580

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Project description:Currently, immunotherapy is widely used in the treatment of various stages of non-small cell lung cancer. According to clinical experience and results of previous studies, immunotherapy as neoadjuvant therapy seems to exhibit better efficacy against early resectable non-small cell lung cancer as compared to advanced lung cancer, which is often defined as unresectable non-small cell lung cancer. However, this observation has not been established in clinical studies. This systematic review aimed to evaluate the efficacy of immunotherapy in early and late lung cancer, wherein objective response rate (ORR) and disease control rate (DCR) were used as evaluation indexes. The present study also evaluated the safety of immunotherapy in early and late lung cancer, wherein the rate of treatment-related adverse reactions (TRAEs) was used as an indicator. Electronica databases, including PubMed, Cochrane Library, Embase, and other databases, were searched to identify relevant studies. Besides this, all the available reviews, abstracts, and meeting reports from the main international lung cancer meetings were searched manually. ORR, DCR, and TRAEs were extracted as the primary outcomes. A total of 52 randomized controlled trials involving 13,660 patients were shortlisted. It was observed that immunotherapy alone significantly improved DCR in early lung cancer in comparison to advanced lung cancer. Importantly, the improvement in ORR was not to the same extent as reported in the case of advanced lung cancer. The combination of immunotherapy with other therapies, especially immunochemotherapy, significantly improved ORR and DCR in early lung cancer. In terms of safety, immunotherapy either alone or in combination with other therapies exhibited a better safety profile in early lung cancer than in advanced lung cancer. Altogether, the benefits of immunotherapy in early lung cancer appeared to be better than those observed in advanced lung cancer, especially with the regard to the regimen of immunotherapy in combination with chemotherapy. In terms of safety, both immunotherapy alone and its combination with chemotherapy were found to be safer in early lung cancer as compared to advanced lung cancer.

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How close are we to customizing chemotherapy in early non-small cell lung cancer?

Publications

How close are we to customizing chemotherapy in early non-small cell lung cancer?

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