Abstract
SummaryNon-small cell lung cancer (NSCLC) treatment was booming at this year’s ASCO 2018 meeting as several well-performed phase III trials with practice-changing potential were presented. Thereby immune checkpoint blockade (ICB) consolidated its major role in the treatment of NSCLC patients without genetic alterations and extended its use by showing impressive data on ICB combination therapies (mainly combined with chemotherapy). Furthermore the role of predictive biomarkers for ICB therapy (Programmed death-ligand 1 [PD-L1] expression, tumor mutational burden [TMB] testing and others) have been further developed and blood-based tests were presented with promising data revealing the potential of this minimally invasive method for treatment monitoring and guidance in the future. Nevertheless the best biomarker is still elusive and future research is ongoing and might be a multimodal approach combining different modalities. No major studies concerning new genetic alterations or innovative targets were presented and the focus in genetic driven NSCLC was the evaluation of combinational approaches (e.g. in epidermal growth factor receptor [EGFR] mutation positve patients, EGFR tyrosine kinase inhibitor [TKI] plus anti-angiogenic agent or chemotherapy backbone). The presented results showed some benefit for the combinational approach; however toxicity might be an issue and further validation is necessary. Summarizing, ASCO 2018 showed that combinational approaches will be the future standard treatment in NSCLC and that biomarker identification is more heterogeneous and complex than anticipated, but presented next generation techniques may pave the way to a more personalized cancer therapy.
Highlights
The therapeutic landscape of lung cancer is changing rapidly due to better characterization of non-small cell lung cancer (NSCLC) genetics and identification of hallmark immunobiological characteristics
In the whole study population (i.e. TPS ≥1%), median Overall survival (OS) was 16.7 months in the pembrolizumabtreated and 12.1 months in those patients treated with chemotherapy (HR 0.81; 95% CI, 0.71–0.93; P = 0.0018)
Results revealed that PD-L1 expression had an impact on Progression-free survival (PFS) in patients treated with immune checkpoint blockade (ICB) harbouring an EGFR mutation or KRAS mutation
Summary
The therapeutic landscape of lung cancer is changing rapidly due to better characterization of non-small cell lung cancer (NSCLC) genetics and identification of hallmark immunobiological characteristics. The results are mainly confirmatory of the previous findings of the KEYNOTE-024 study [3]; the study opens, due to a more favorable toxicity profile (grade 3 to 5 adverse events 17.8% vs 41.0%) in PDL1 1–49% patients a new treatment option with pembrolizumab monotherapy This strategy has to be evaluated carefully as several new combinational trials have been presented and will be summarized in the following. ABCP improved median progression-free survival (PFS) by 1.5 months compared with BCP (8.3 vs 6.8 months; HR, 0.59 in the ITT wildtype population). For advanced squamous NSCLC novel therapeutic options are of high medical need and at ASCO 2018 two promising phase III studies (IMpower131 and KEYNOTE-407) have been presented testing chemotherapy backbone combined with IO therapy [4, 6].
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