Recent Advances in NSCLC Treatment Aug 10, 2016 魏裕峰 義大醫院胸腔內科

Management of Lung Cancer Surgery Chemotherapy Radiotherapy Target therapy Immumotherapy Multidisciplinary treatment of lung cancer

Mechanisms of chemotherapy and target therapy Target rapidly dividing cells Target therapy Interfere with key molecular events in tumor cells that drive tumor growth and invasion (signal transduction)

Historical milestones in the treatment for NSCLC

Basic Formula of Chemotherapy in Lung Cancer Platinum + Partner +/- Biologic Pemetrexed Gemcitabine Docetaxel Paclitaxel Vinorelbine Etoposide Cisplatin Carboplatin Bevacizumab (Cetuximab)

Nature Clinical Practice Oncology (2007) 4, 86-100

First line chemotherapy in advanced NSCLC ECOG1594, N Engl J Med 2002;346:92-8

J Clin Oncol 2008;26:3543–51

J Thorac Oncol. 2010;5: 688–695

Target Therapy

In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a fi rst-line therapy until disease progression or unacceptable toxicity. Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the effi cacy analyses. Primary end point: PFS

Progression Free Survival

Overall Survival

Adverse Events Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC.

Antiangiogenic TKIs for NSCLC

Nintedanib (formerly BIBF 1120; Boehringer Ingelheim, Ingelheim, Germany) is a potent, oral angiokinase inhibitor that targets the pro-angiogenic pathways mediated by VEGFR1–3, fi broblast growth factor receptors (FGFR) 1–3, and platelet-derived growth factor receptors (PDGFR) α and β. Between Dec 23, 2008, and Feb 9, 2011, 655 patients were randomly assigned to receive docetaxel plus nintedanib and 659 to receive docetaxel plus placebo.

Including Taiwan Background Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. Between Dec 3, 2010, and Jan 24, 2013, we screened 1825 patients, of whom 1253 patients were randomly allocated to treatment.

Immunotherapy Checkpoint inhibitor Relieve inhibition of the immune system that allows tolerance of tumor growth Aid in the recognition of cancer as foreign by immune system Stimulate immune response

Immunotherapy (Immune) checkpoint inhibitor Cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody Programmed death receptor 1 (PD1) antibody Programmed death ligand 1 (PDL1) antibody

(Immune) checkpoint inhibitor CTLA-4 antibody (Anti-CTLA-4) Ipilimumab Tremelimumab PD1 antibody (Anti-PD-1) Nivolumab (CheckMate series) Pembrolizumab (KeyNote series) PDL1 antibody (Anti-PDL-1) Atezolizumab (MPDL3280A) Durvalumab (MEDI4736)

Questions in Second and Subsequent Lines of Therapy Presented By Martin Edelman at 2015 ASCO Annual Meeting

Presented By Grace Dy at 2015 ASCO Annual Meeting SUMMARY Personalized Treatment Era… Presented By Grace Dy at 2015 ASCO Annual Meeting