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New therapeutic approaches in lung cancer

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Presentation on theme: "New therapeutic approaches in lung cancer"— Presentation transcript:

1 New therapeutic approaches in lung cancer
Dr Marc Lambrechts

2 Anti-cancer strategies for NSCLC today
Traditional therapies Targeted therapies Adjuvant chemotherapy improves survival in early stage NSCLC Addition of targeted therapies to 1st-line chemotherapy Chemo-radiotherapy improves survival in advanced NSCLC Use of EGFR tyrosine kinase inhibitors in advanced disease Modest but significant benefits Targeted populations NOTES to Dr Lambrechts Discuss current therapeutic options for advanced NSCLC and identify the unmet need Has reached plateau Significant side-effects There is a need for new treatment options that prolong survival and improve quality of life in this group of patients

3 Immunotherapy Immunotherapy The immune system
Activates natural immune system Body’s natural defence mechanism Recognises foreign and harmful agents (e.g. viruses, bacteria, etc) Helps body identify cancer cells NOTES to Dr Lambrechts Mention what is immunotherapy and how is “boosts” the body’s natural immune system. Boosts immune response against cancer Initiates response to eliminate potential threats

4 Rationale for therapeutic cancer vaccines
Evidence for the ability of the immune system to recognize tumors Wide range of newly identified potential tumor targets Favourable toxicity profile Possible immuno-stimulating effects of existing therapies Preventive cancer vaccines Therapeutic cancer vaccines Used BEFORE the disease is established Used AFTER the disease is established NOTES to Dr Lambrechts Mention what are “Therapeutic Cancer Vaccines” and why are they an attractive option for cancer therapy. Differentiate between “preventive” and “therapeutic” vaccines and mention some examples. Stimulate the immune system to target INFECTIOUS agents Stimulate the immune system to target CANCER cells Used to PREVENT the disease Used to TREAT the disease Echchakir H, et al. Int Immunol 2000;12:537–546 Wei YQ, et al. Immunol Invest 1989;18:1095–1105

5 Identifying a vaccine target/antigen
Tumor antigens in lung cancer GD3 MAGE-A3 MUC1 MUC1 tumor antigen NOTES to Dr Lambrechts Briefly discuss why MUC1 is a good target for therapeutic cancer vaccines Associated with increased risk of disease progression and poor prognosis Suppresses immune cell function Can prevent anti-tumor immune response

6 MUC1 expression in lung cancer
Tumor type MUC1 expression No. of tissues Reference Breast 91 % 1447 Rakha et al (2005) NSCLC 99 % 231 Merck Serono. Data on file Renal cell carcinoma 84 % 133 Langner et al (2004) Colorectal 81 % 243 Baldus et al (2002) Ovarian 83 % 63 Chauhan et al (2006) SCCHN 82 % 29 Croce et al (2001) Nasopharyngeal 100 % 38 Zhong et al (1993) Gastric 77 % 136 Utsunomiya et al (1998) Prostate 79 % 89 DeNardo et al (2005) Pancreatic 53 Qu et al (2004) Mesothelioma 75 % 20 Saad et al (2005) Multiple myeloma 73 % 26 Cloosen et al (2006) Esophagus 32 % Kijima et al (2001)

7 Lung cancer vaccine trials
Results 917 studies with “cancer vaccines” 59 studies in NSCLC 22 studies active NOTES to Dr Lambrechts This is an overview of all the vaccine trials in NSCLC (as listed on 3 agents in Phase III trials BLP25 Liposome Vaccine (START trial) MAGE-A3 (MAGRIT trial) Belagenpumatucel-L (STOP trial)

8 Phase III therapeutic cancer vaccine trials in NSCLC
BLP25 Liposome Vaccine Antigen Antigenic MUC1 peptide Vaccine containing a synthetic antigen, designed to stimulate the immune system against cells containing that antigen. BLP25 Liposome Vaccine is currently under clinical investigation and has not been approved for use in the US, Europe, Canada, or elsewhere. BLP25 has not been proven to be either safe or effective and any claims of safety and effectiveness can be made only after regulatory review of the data and approval of the labelled claims

9 BLP25 Phase II results: Stage IIIb locoregional patients
Overall survival Safety results Most adverse events were disease related and unrelated to the study drug Mild-to-moderate flu-like symptoms and injection site redness (i.e. cough, fatigue, nausea,vomiting, diarrhea) Ten patients have been treated for up to 8.2 years and eight are still being treated NOTES to Dr Lambrechts The results observed in the subgroup of patients from the Phase II trial where overall survival was 30.6 months compared to 13.3 months in the control. Highlight the favourable side effects profile and the fact that some patients are still alive and being treated with BLP25 today. In a subset of patients, BLP25 showed more than a doubling of the median survival time from 13.3 to 30.6 months and a favorable tolerability profile. Butts C, et al. J Clin Oncol 2005;23:6674–6681; Butts C, et al. J Thorac Oncol 2007;2(Suppl 4):S332-S333. Abstract No: B1-01.

10 Phase III therapeutic cancer vaccine trials in NSCLC
BLP25 Liposome Vaccine MAGE-A3 Immunotherapeutic Antigen Purified MAGE-A3 protein Vaccine containing a synthetic antigen, designed to stimulate the immune system against cells containing that antigen.

11 MAGE-A3 Phase II results
Disease-free survival Overall survival HR = 0.73 (95% CI ) one-sided logrank p = 0.093 HR = 0.66 (95% CI ) one-sided logrank p = 0.088 NOTES to Dr Lambrechts Briefly discuss Phase II results MAGE-A3 immunotherapeutic showed a trend toward increasing overall and disease-free survival compared to placebo.

12 Phase III therapeutic cancer vaccine trials in NSCLC
BLP25 Liposome Vaccine MAGE-A3 Immunotherapeutic Belagenpumatucel-L Antigen Tumor cells from four irradiated NSCL cancer cell lines Genetically engineered to inhibit TGF-β2 which plays a role in suppressing the immune system.

13 Belagenpumatucel-L Phase II results
Radiographic evidence Overall survival NOTES to Dr Lambrechts Briefly discuss these Phase II results in terms of OS and the radiographic evidence. (n=61, p=0.0186) Pre-therapy Post-therapy Belagenpumatucel-L showed a positive effect on overall survival and tumor response as shown by the radiographic evidence.

14 Phase III vaccine trials in NSCLC
START trial MAGRIT trial STOP trial BLP25 MAGE-A3 Belagenpumatucel-L Patients with unresectable stage III NSCLC following chemoradiotherapy Resected patients with stage Ib, II or IIIa, MAGE-A3 positive NSCLC Patients with Stage IIIa or IIIb/IV NSCLC that respond to st-line therapy 1,322 patients 2,270 patients 700 patients BLP25 + BSC MAGE-A3 Vaccine + BSC NOTES to Dr Lambrechts Overview of Phase III trials in NSCLC involving therapeutic cancer vaccines. or or or Placebo + BSC Placebo Placebo + BSC 1ry Objective 1ry Objective 1ry Objective OS PFS PFS + OS

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