有效的非小细胞肺癌治疗的基础-Nicholas Thatcher-2009CSCO年会.ppt

salvage slides Building?the?foundations?of?effective?NSCLC?therapy Prof. Nicholas Thatcher Christie Hospital NHS Trust, U.K. AVASTIN FIRST LINE NON-SQUAMOUS ADVANCED NSCLC Introduction, anti angiogenesis Phase III trials, E4599, AVAIL Phase IV trial, SAIL Future Conclusion ANGIOGENESIS INHIBITION THROUGH THE VEGF PATHWAY ANTI-VEGF THERAPY: MECHANISM OF ACTION EFFECTS OF VEGF INHIBITION:inhibition of recurrent vessel growth PIVOTAL STUDIES OF AVASTIN IN COMBINATION WITH PLATINUM-CONTAINING CHEMOTHERAPY PHASE III TRIALS OF AVASTIN (E4599 VS. AVAIL): ELIGIBILITY CRITERIA AND SAFETY E45991 and AVAiL2 evaluated Avastin in combination with CP and CG, respectively Inclusion/exclusion criteria were comparable, with additional considerations in AVAiL ECOG PS 0-1 ; Non-squamous cell no haemoptysis, 1/2 tsp bright red blood ;CNS metastases; thrombotic ,bleeding disorders; anticoagulants ,aspirin, NSAIDs; significant cardiovascular disease No evidence of tumour invading or abutting major blood vessels; no spinal cord compression; ulceration, bone fractures or wound-healing complications AVASTIN-BASED THERAPY UNTIL PROGRESSIONIMPROVES RR: E4599 AND AVAIL E4599: OVERALL SURVIVAL, PROGRESSION-FREE SURVIVAL AND RESPONSE RATE ADVANTAGE UNPRECEDENTED OS BENEFIT IN PATIENTS WITH ADENOCARCINOMA HISTOLOGY AVAIL: PROGRESSION-FREE SURVIVAL AND RESPONSE RATE ADVANTAGE AVAIL: FOREST PLOT OF HR FOR PROGRESSION-FREE SURVIVAL BY SUBGROUP (PLACEBO + CG VS AVASTIN 7.5mg/kg + CG) BEVACIZUMAB PATHOLOGICAL SELECTIONREDUCES BLEEDING RISK SAFETY PROFILE OF AVASTIN IN NSCLC IS WELL-CHARACTERISED The side-effect profile of Avastin in patients with advanced NSCLC is generally consistent with that observed in other solid tumour types Hypertension and proteinuria were the most common side effects associated with Avastin in E45991 and AVAiL2 these events were generally manageable and did not require permanent dis