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ALK inhibition, guidelines, liquid biopsies, and immunotherapy

Presented by
Dr Céline Mascaux, Aix-Marseille University, France
Conference
ERS 2018
Trial
AURA3, FLAURA
The development of ALK inhibition went faster than EGFR inhibition. Currently, there are several options for the first-line treatment of ALK-positive NSCLC: first crizotinib [5], then ceritinib [6], and finally alectinib, which was studied in two patient populations: in Japan [7] and in Europe and the United States [8]. The guidelines of the National Comprehensive Cancer Network (NCCN) advise first to establish the histological subtype of the tumour with adequate tissue for molecular testing and to consider re-biopsy if appropriate. The recommended molecular tests depend on the tumour type (see Table) [9].


Table: NCCN guidelines recommendations [9].

ERS 2018 - oncology: Table 1. NCCN guidelines recommendations [9]

Another subject Dr Mascaux discussed was the development of liquid biopsies, which determines the presence of circulating tumour cells in the blood [10]. This diagnostic tool is easy for both patient and doctor. In the AURA3 and FLAURA studies with osimertinib, tumour cells in the blood and in the tissue showed a high concordance with respect to their molecular biology. “However, a negative blood test could be false negative, so a tissue sample should still be analysed.”

Immunotherapy

Next to targeted therapies, another important development in the treatment of lung cancer, is that of immunotherapy. These drugs are directed either against PD-L1 which is expressed on T-cells, or PD-1 on tumour cells [11]. “In some patients, immunotherapy results in a durable response which can endure years after stopping the drug”, stated Dr Mascaux. “The more mutations are present in the tumour (i.e. higher mutational load), the better the response to immunotherapy. We need better biomarkers to predict the sensitivity for immunotherapy. Furthermore, combination therapy is needed to combat the heterogeneity of the tumour.”


  1. Solomon BJ, et al. N Engl J Med. 2014;371:2167-77.
  2. Shaw AT, et al. Lancet Oncol. 2017;18:874-886.
  3. Hida T, et al. Lancet. 2017;390:29-39.
  4. Peters S, et al. N Engl J Med. 2017;377:829-838.
  5. NCCN Clinical practice guidelines for NSCLC. 2017. www.nccn.org.
  6. Crowley E, et al. Nat Rev Clin Oncol. 2013;10:472-84.
  7. Herbst RS, et al. Nature. 2018;553:446-454.




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