Presentation on theme: "New therapeutic approaches in lung cancer"— Presentation transcript:
1New therapeutic approaches in lung cancer Dr Marc Lambrechts
2Anti-cancer strategies for NSCLC today Traditional therapiesTargeted therapiesAdjuvant chemotherapy improves survival in early stage NSCLCAddition of targeted therapies to 1st-line chemotherapyChemo-radiotherapy improves survival in advanced NSCLCUse of EGFR tyrosine kinase inhibitors in advanced diseaseModest but significant benefitsTargeted populationsNOTES to Dr LambrechtsDiscuss current therapeutic options for advanced NSCLC and identify the unmet needHas reached plateauSignificant side-effectsThere is a need for new treatment options that prolong survival and improve quality of life in this group of patients
3Immunotherapy Immunotherapy The immune system Activates natural immune systemBody’s natural defence mechanismRecognises foreign and harmful agents (e.g. viruses, bacteria, etc)Helps body identify cancer cellsNOTES to Dr LambrechtsMention what is immunotherapy and how is “boosts” the body’s natural immune system.Boosts immune response against cancerInitiates response to eliminate potential threats
4Rationale for therapeutic cancer vaccines Evidence for the ability of the immune system to recognize tumorsWide range of newly identified potential tumor targetsFavourable toxicity profilePossible immuno-stimulating effects of existing therapiesPreventive cancer vaccinesTherapeutic cancer vaccinesUsed BEFORE the disease is establishedUsed AFTER the disease is establishedNOTES to Dr LambrechtsMention 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 agentsStimulate the immune system to target CANCER cellsUsed to PREVENT the diseaseUsed to TREAT the diseaseEchchakir H, et al. Int Immunol 2000;12:537–546 Wei YQ, et al. Immunol Invest 1989;18:1095–1105
5Identifying a vaccine target/antigen Tumor antigens in lung cancerGD3MAGE-A3MUC1MUC1 tumor antigenNOTES to Dr LambrechtsBriefly discuss why MUC1 is a good target for therapeutic cancer vaccinesAssociated with increased risk of disease progression and poor prognosisSuppresses immune cell functionCan prevent anti-tumor immune response
6MUC1 expression in lung cancer Tumor typeMUC1 expressionNo. of tissuesReferenceBreast91 %1447Rakha et al (2005)NSCLC99 %231Merck Serono. Data on fileRenal cell carcinoma84 %133Langner et al (2004)Colorectal81 %243Baldus et al (2002)Ovarian83 %63Chauhan et al (2006)SCCHN82 %29Croce et al (2001)Nasopharyngeal100 %38Zhong et al (1993)Gastric77 %136Utsunomiya et al (1998)Prostate79 %89DeNardo et al (2005)Pancreatic53Qu et al (2004)Mesothelioma75 %20Saad et al (2005)Multiple myeloma73 %26Cloosen et al (2006)Esophagus32 %Kijima et al (2001)
7Lung cancer vaccine trials Results917 studies with “cancer vaccines”59 studies in NSCLC22 studies activeNOTES to Dr LambrechtsThis is an overview of all the vaccine trials in NSCLC (as listed on3 agents in Phase III trialsBLP25 Liposome Vaccine (START trial)MAGE-A3 (MAGRIT trial)Belagenpumatucel-L (STOP trial)
8Phase III therapeutic cancer vaccine trials in NSCLC BLP25 Liposome VaccineAntigenAntigenic MUC1 peptideVaccine 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
9BLP25 Phase II results: Stage IIIb locoregional patients Overall survivalSafety resultsMost adverse events were disease related and unrelated to the study drugMild-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 treatedNOTES to Dr LambrechtsThe 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.
10Phase III therapeutic cancer vaccine trials in NSCLC BLP25 Liposome VaccineMAGE-A3 ImmunotherapeuticAntigenPurified MAGE-A3 proteinVaccine containing a synthetic antigen, designed to stimulate the immune system against cells containing that antigen.
11MAGE-A3 Phase II results Disease-free survivalOverall survivalHR = 0.73 (95% CI ) one-sided logrank p = 0.093HR = 0.66 (95% CI ) one-sided logrank p = 0.088NOTES to Dr LambrechtsBriefly discuss Phase II resultsMAGE-A3 immunotherapeutic showed a trend toward increasing overall and disease-free survival compared to placebo.
12Phase III therapeutic cancer vaccine trials in NSCLC BLP25 Liposome VaccineMAGE-A3 ImmunotherapeuticBelagenpumatucel-LAntigenTumor cells from four irradiated NSCL cancer cell linesGenetically engineered to inhibit TGF-β2 which plays a role in suppressing the immune system.
13Belagenpumatucel-L Phase II results Radiographic evidenceOverall survivalNOTES to Dr LambrechtsBriefly discuss these Phase II results in terms of OS and the radiographic evidence.(n=61, p=0.0186)Pre-therapyPost-therapyBelagenpumatucel-L showed a positive effect on overall survival and tumor response as shown by the radiographic evidence.
14Phase III vaccine trials in NSCLC START trialMAGRIT trialSTOP trialBLP25MAGE-A3Belagenpumatucel-LPatients with unresectable stage III NSCLC following chemoradiotherapyResected patients with stage Ib, II or IIIa, MAGE-A3 positive NSCLCPatients with Stage IIIa or IIIb/IV NSCLC that respond to st-line therapy1,322 patients2,270 patients700 patientsBLP25 + BSCMAGE-A3Vaccine + BSCNOTES to Dr LambrechtsOverview of Phase III trials in NSCLC involving therapeutic cancer vaccines.orororPlacebo + BSCPlaceboPlacebo + BSC1ry Objective1ry Objective1ry ObjectiveOSPFSPFS + OS