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ECCO 2017 webcasts - Part 5
"Medical management of advanced NSCLC" by Christian Manegold
Medical Faculty Mannheim/University of Heidelberg
Dr Manegold reviews the testing of antiangiogenic agents over the past decade, noting that 3 out of 10 agents are approved for clinical use: bevacizumab, ramucirumab and nintedanib. He presents an algorithm showing current treatment regimens in non-small cell lung cancer (NSCLC) wild type and mutant tumours.
Bevacizumab can be used in combination with platinum-based chemotherapy in first-line treatment for advanced nonsquamous (NS)-NSCLC until progression. Adding bevacizumab increases response rate, progression-free survival and overall survival compared to a carboplatin-paclitaxel regimen. However, its safety profile means that it may not be an appropriate treatment for everyone.
Trials using ramucirumab or nintedanib plus docetaxel as a second-line therapy for advanced NSCLC both showed improvements in progression-free survival and overall survival versus single agent docetaxel.
An issue with currently approved antiangiogenic therapies is the lack of a biomarker that can be used to help predict patient response.
There are many ongoing clinical trials investigating antiangiogenesis coupled with other targeted agents for advanced NSCLC (e.g., combinations of bevacizumab with erlotinib, gefitinib, alectinib or crizotinib). The rationale for such trials are: the agents target different molecular pathways of tumourigenesis, clinical and non-clinical data show they have additive anti-tumour efficacy, they are generally well tolerated, and they have been integrated into the NSCLC treatment algorithm.
The approval of first-line bevacizumab plus erlotinib in NS-NSCLC tumours with EGFR mutations is based on the JO25567 clinical trial, which demonstrated a substantial increase in mean progression-free survival.
Two immune-checkpoint inhibitors that target programmed cell death 1 ligand (PD-1), nivolumab and pembrolizumab, have been approved in the USA and the EU. Both showed efficacy as measured by response rate, progression-free survival and overall survival in various patient populations. Dr Manegold sees this as an exciting opportunity to pair these immune-checkpoint inhibitors with antiangiogenic therapies, citing the evidence that: antiangiogenic therapies stimulate immune response and enhance the efficacy of immunotherapy, immunotherapy can be antiangiogenic, both operate synergistically without a substantial increase in toxicity, and preclinical evidence supports increased efficacy.
Dr Manegold closes his talk by stating there is still much to do in the area of antiangiogenic therapy combined with immunotherapy, addressing toxicity, patient selection, general efficacy predictions, prediction of efficacy by PD-L1 expression level,PD-L1 test standardization and validation.