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C. Belani



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    MS20 - Small Cell Lung Cancer (ID 37)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Medical Oncology
    • Presentations: 1
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      MS20.1 - The Clinical Challenge of Small Cell Lung Cancer (ID 551)

      14:05 - 14:25  |  Author(s): C. Belani

      • Abstract
      • Presentation
      • Slides

      Abstract
      Small cell lung cancer represents about 12% of new case of lung cancer in the USA. It has a unique presentation and natural history compared to other types of lung cancer and is highly responsive to first-line treatment. Unfortunately, the cancer typically relapses after a short period of time and exhibits resistance to cytotoxic and targeted therapeutic agents with a poor median survival. The last 2 decades witnessed significant improvement in our understanding of the molecular basis of small cell lung cancer with identification of several potential therapeutic targets leading to application and evaluation of novel chemotherapeutic, targeted and immunotherapeutic agents in a large number of clinical trials. In this presentation, we will summarize the data from the recent and ongoing clinical trials in this disease and understand the challenge that it poses. However, the results have overall been disappointing and the combination of a platinum compound with etoposide remains the most effective treatment for this patient population. Despite the advent of new cytotoxic and targeted agents, which have shown significant activity in other types of cancer including non-small cell lung cancer, their use in SCLC has not had any impact on survival. The differences in efficacy observed with agents such as amrubicin and irinotecan in patients from different ethnic or racial groups indicate the importance of the understanding the tumor genetic makeup and individualizing treatment regimens. The landscape of genetic alterations of SCLC is more complex than in other types of cancer. To date, no specific mutation, abnormal fusion protein secondary to chromosomal translocation or aberrant signal transduction pathway has been validated and proven to be critical for the continuation of the carcinogenesis process and survival of the SCLC tumor cells. SCLC remains one of the most challenging tumors to treat with our current standard of care. The recent advances in sequencing and high throughput technologies have started to yield useful information about the molecular abnormalities of SCLC. We need to refine the recently acquired knowledge of SCLC biology and apply that knowledge in innovative clinical trials to have a breakthrough in the treatment of SCLC.

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    PL05 - Genomics: From Research Tool to the Lung Cancer Clinic (ID 76)

    • Event: WCLC 2013
    • Type: Plenary Session
    • Track: Pathology
    • Presentations: 1
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      PL05.3 - Challenges for the Clinician (ID 798)

      17:10 - 17:35  |  Author(s): C. Belani

      • Abstract
      • Slides

      Abstract
      . Although EGFR mutations and fusions involving ALK and ROS1 are targetable by currently approved agents, these alterations are present in less than a fifth of patients with non-squamous NSCLC. Treatment options for the majority of patients remain largely empirical. The urgent need to develop therapies capable of targeting cancers without these alterations can only occur with a better understanding of the molecular biology and cytogenetic alterations. Recently, the lung cancer mutation consortium reported longer survival in patients with adenocarcinoma who underwent multiplexed genomic testing for the detection of alterations in 10 genes, and subsequently received matched targeted treatments. [Johnson et al J Clin Oncol 31, 2013 (suppl; abstr 8019)]. A total of 1,007 patients were screened for at-least one genetic alteration, and an actionable alteration that led to the use of targeted therapies was detected in 28% of these patients. The median survival in these patients was 3.5 years, while patients whose tumors did not harbor actionable alterations had a median survival of 2.1 years. It would be reasonable to assume that adapting NGS technologies, which allow comprehensive screening of the entire genome at a higher resolution, will result in improved outcomes in patients whose tumors do not harbor targetable mutations identifiable by commercially available assays. NGS has allowed a better characterization of lung cancer, with the identification of novel mutations and copy number alterations. Preliminary results from TCGA demonstrated that a significant percentage of patients with lung cancer harbor a targetable abnormality. It is still possible that additional less common mutations or alterations will be discovered once the sequencing of 1000 lung cancer samples is completed by TCGA. The next challenge is the development of novel drugs based on specific targetable abnormalities. Although this strategy may require extensive evaluation and multiple trials targeting distinct molecular subtypes of tumors, this departure from the empirical treatment of lung cancer, probably represents the best hope towards achieving meaningful progress.

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