• Save
MON 2011 - Slide 24 - R.A. Stahel - NSCLC systemic therapy
Upcoming SlideShare
Loading in...5
×
 

Like this? Share it with your network

Share

MON 2011 - Slide 24 - R.A. Stahel - NSCLC systemic therapy

on

  • 1,514 views

 

Statistics

Views

Total Views
1,514
Views on SlideShare
1,514
Embed Views
0

Actions

Likes
0
Downloads
0
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

MON 2011 - Slide 24 - R.A. Stahel - NSCLC systemic therapy Presentation Transcript

  • 1. Evolution of systemic therapy for non-small cell lung cancer:From empiric to molecular-driven approach
    Rolf Stahel
    University Hospital
    Zürich
    Switzerland
    Ermatingen, April 6, 2010
  • 2. Past developments in advanced NSCLC
    Cisplatin-based combination prolongs survival Edna Rapp, JCO 1988
    Reduced nausea and vomiting with ondansetron Ann Intern Med 1990
    Meta-analysis using data on individual patients from 52 randomized trials definitively confirms survival advantage Non-small cell lung cancer collaborative group, BMJ 1995
    Similar results with platin combined with any third generation agent: a plateau has been reachedSchiller, NEJM 2001
    2nd line chemotherapy with docetaxel, pemetrexedShepherd, JCO 2000; Hanna, JCO 2004
  • 3. Case 1: Presentation
    58-y/o woman, married, no children, works as executive secretary suffers from back pain since December 2008. After 2 months unsuccessful treatment by a chiropractioner, her family doctor orders an MRI. Here, a tumor leading to destruction of the first lumber vertebra was identified and the patient referred to oncology.
    The medical history and physical examination is otherwise unrevealing, patients stopped smoking 30 years ago
  • 4. Case 1: CT at presentation
  • 5. Case 1: Diagnosis and therapy
    Howtoproceed?
    18.2.2009 Surgicaldecompressionand dorsal stabilisation
    Histology: Adenocarcinoma, TTF-1 positive, ER negative
    Diagnosis: Adenocarcinomaofthelungwith mediastinal andcervicallymphnodemetastasisandbonemetastasis
    Howtotreat?
  • 6. Case 1: Diagnosis and therapy
    23.2.2009 Initiation of chemotherapy with cisplatin, pemetrexed and bevacizumab, well tolerated
    16.3. Hospitalization for second cycle. Updated results of pathology:
    EGFR genotype (exons 18 bis 21): Deletion in exon 19 (p.746E_750Adel) EGFR-FISH: positive (high-grade polysomy)EGFR-IHC: protein expression score 3 (DAKO Score 0-3)
    Continuation of cisplatin, pemetrexed, bevacizumab for total of 4 cycles
  • 7. Evolution of systemic therapy for non-small cell lung cancer:
    Advanced NSCLC:Histological classification is necessary for decision making
    Advanced NSCLC: Reconsideration of extended therapy
    Molecular classification: Present necessities and future directions
    Consequences for second line therapy
    Consequences for adjuvant therapy
  • 8. 1. Histological classification is necessary for today‘s decision making
    A diagnosis of “non-small cell lung cancer” is no longer acceptable as sufficient basis for treatment decisions:
    Cisplatin superior to carboplatin in adenocarcinoma Ardizzoni, JNCI 2007
    Benefit of bevacizumab added to first line chemotherapy in non-squamous cell carcinoma Sandler, JCO 2006; Reck JCO 2009
    Differential effect of pemetrexed in non-squamous vs squamous cell carcinoma Scagliotti, JCO 2008
    Histology will help guide decision about which molecular analysis is performed
  • 9. Immunohistochemistry of NSCLC
    TTF-1
    Surfactant apoproteins (A+B)
    Napsin A
    CK7
    p63
    HMWCK (CK5-6, 34βE12)
    Desmocollin 3
    Adenocarcinoma
    Squamous cell carcinoma
  • 10. Meta-analysis: Cisplatinvs carboplatin-based chemotherapy
    • Ardizzoni, JNCI 2007
  • Cisplatin-Pemetrexed vs Cisplatin-Gemcitabine in Advanced NSCLC
    No difference in overall
    PFS or survival between
    study arms
    Cis/pem improves survival over cis/gem
    in non-squamous cell carcinoma (HR 0.81, p=0.005)
    Cis/gem improves survival over cis/pem
    in squamous cell carcinoma (HR 1.23, p=0.05)
    Scagliotti, JCO 2008
  • 11. Bevacizumab added to chemotherapy:Design of 2 phase III trials
    E45991
    CP x 6 (n=444)
    Previously untreated, stage IIIB, IV or recurrent non-squamous NSCLC
    (n=878)
    PD
    Bevacizumab (15mg/kg) every 3 weeks + CP x 6 (n=434)
    Bev
    PD
    Primary endpoint: OS
    Bevacizumab (15mg/kg) every 3 weeks + CG x 6 (n=351)
    Bev
    2
    RANDOMISE
    PD
    AVAiL2
    1
    Placebo (15mg/kg) +CG x 6
    Previously untreated, stage IIIB, IV or recurrent non-squamous NSCLC (n=1,043)
    Placebo
    PD
    (n=347)
    1
    Placebo (7.5mg/kg) +CG x 6
    Primary endpoint: PFS
    Bevacizumab (7.5mg/kg) every 3 weeks + CG x 6 (n=345)
    Bev
    2
    PD
    CP = carboplatin/paclitaxel
    CG = cisplatin/gemcitabine
    Sandler, 2006; Reck, JCO 2009
  • 12. Bevacizumab added to chemotherapy:Significant increase of response
    Sandler, 2006; Reck, JCO 2009
  • 13. Bevacizumab added to chemotherapy: Significant Increase of PFS
    PFS in E45991
    PFS in AVAiL2
    1.0
    0.9
    0.8
    0.7
    0.6
    0.5
    0.4
    0.3
    0.2
    0.1
    0
    1.0
    0.9
    0.8
    0.7
    0.6
    0.5
    0.4
    0.3
    0.2
    0.1
    0
    Bev 7.5mg/kg + CG
    Bev 15mg/kg + CP
    CP
    Bev 15mg/kg + CG
    Placebo + CG
    Probability of PFS
    0 6 12 18 24 30
    0 6 12 18 24 30
    Duration of PFS (months)
    Duration of PFS (months)
    Median PFSBev 15mg/kg
    Median PFSBev 7.5mg/kg
    Median PFSBev 15mg/kg
    6.2 months
    HR=0.66
    p<0.001
    6.7 months
    HR=0.75
    p=0.003
    6.5 months
    HR=0.82
    p=0.03
    Sandler, 2006; Reck, JCO 2009
  • 14. OS benefit in adenocarcinoma histology: Pre-planned subgroup analysis (E4599)
    Bevacizumab-based therapy (n=602)
    extends OS to 14.2 months
    31% reduction in the risk of death (HR=0.69)
    1.0
    0.75
    0.50
    0.25
    0
    Avastin + CP (n=300)
    CP (n=302)
    Probability of OS
    10.3
    14.2
    0 6 12 18 24 30 36 42 48
    Duration of OS (months)
    Pre-planned subgroup analysis (E4599)
    Sandler, JTO 2008
  • 15. Case 1: Response assessment after 4 cycles of therapy
    February 09
    June 09
  • 16. Case 1: How to proceed
    Systemic therapy:
    Discontinue therapy?
    Maintain pemetrexed?
    Maintain bevacizumab?
    Change to erlotinib?
    Other:
    Radiotherapy to lumber spine?
    Bisphosponates or denosumab?
    Maintenance bevacizumab monthly
  • 17. 2. Advanced NSCLC: Reconsideration of extended therapy
    Significant prolongation of PFS by extended chemotherapy Soon, JCO 2009
    Significant improvement OAS with pemetrexed maintenance after standard cisplatin-based combination chemotherapy (without pemetrexed) in patients with non-squamous cell lung cancerCiuleanu, Lancet 2009
    Significant prolongation of OAS with erlotinib maintenance after standard chemotherapy, independent of histology Cappuzzo, Lancet Oncology 2010
    In booth studies benefit in particular for patients with stable disease
  • 18. Increased time to PD
    Maintenance approach
    Maintenance therapy
    PD
    PD
    Diagnosis
    CR/PR/SD
    Maintenance in advanced NSCLC: treating before disease progression
    First-line treatmentPlatinum doublet chemotherapy
    (4–6 cycles)
    Traditional approach
    2nd/3rd line treatment
    Break from treatment
    Diagnosis
    PD
    PD
    CR/PR/SD
  • 19. Cisplatin based chemotherapy in NSCLC: 2 + 2 vs 2 + 4 cycles
    TTP
    OAS
    Park, JCO 2007
  • 20. Duration of therapy in advanced NSCLC: Progression-free survival
    Gem
    Doc
    Soon, JCO 2009
  • 21. Pemetrexed 15.5 mos
    Pemetrexed 9.9 mos
    Placebo
    10.3 mos
    Placebo
    10.8 mos
    Maintenance pemetrexed vs placebo:Overall survival by histology
    Non-squamous (n=481)
    Squamous (n=182)
    HR=0.70 (95% CI: 0.56-0.88)
    P =0.002
    HR=1.07 (95% CI: 0.49–0.73)
    P =0.678
    Survival Probability
    Time (months)
    Time (months)
    Belani, ASCO 2009; Ciuleanu, Lancet 2009
  • 22. SATUTRN: OAS with erlotinib maintanance in EGFR WT tumors
    Erlotinib
    150mg/day
    PD
    Chemonaïve advanced NSCLC
    n=1,949
    4 cycles of 1st-line platinum-based doublet
    Non-PD
    n=889
    1:1
    Placebo
    PD
    Mandatory tumour sampling
    Maintenance treatment with erlotinib (SATURN)
    Cappuzzo,. Lancet Oncol 2010
  • 23. SATURN: OS in EGFR WT group with SD on first-line chemotherapy
    1.0
    0.8
    0.6
    0.4
    0.2
    0
    Erlotinib (n=114)
    Placebo (n=103)
    HR=0.65 (0.48–0.87)
    Log-rank p=0.0041
    OS probability
    8.7
    12.4
    0 3 6 9 12 15 18 21 24 27 30 33 36
    Time (months)
    Measured from time of randomisation into the maintenance phase
    Coudert, ECLC 2010
  • 24. 0.4
    0.6
    0.8
    1.0
    1.4
    1.2
    Both pivotal maintenance studies suggestgreater benefit in patients with SD vs PR/CR
    JMEN OS Pemetrexed
    SATURN OS Erlotinib
    ITT population (n=663)
    CR/PR (n=322)
    SD (n=337)
    ITT population(n=889)
    CR/PR (n=394)
    SD (n=487)
    0.4
    0.8
    0.6
    1.0
    1.4
    1.2
    HR
    HR
    Favours erlotinib
    Favours placebo
    Favours placebo
    Favours pemetrexed
  • 25. Case 1: Follow-up on bevacizumab
    March 10
    June 09
    October 09
  • 26. 3. Molecular classification: Present necessities and future directions
    Adenocarcinoma of the lung is not a uniform disease and needs to be classified by additional molecular analysis
    Present needs include EGFR mutation status and determination of EML4-ALK fusion gene
    Knowledge about resistance mechanisms to available agents and the opportunity of agents against new molecular targets mandate change in the trial design
    Potential driver mutations are also being identified in squamous cell lung cancer
  • 27. Mutations identified in EGFR gene
    Confer sensitivity/resistance to EGFR TKIs
    Unclear effect on sensitivity to EGFR TKIs
    EGFR transcript
    L688P
    V689M
    I715S
    L718P
    S720X
    18
    P694X
    V700D
    E709X
    18
    Exons 1–16
    G719A/S
    G735S
    V738F V742A
    T751IS752Y
    D761N
    Deletions
    L730F P733L
    E746K
    19
    Exon 17
    D761Y
    A763V
    N765A
    S768I
    T783A
    L792P
    L798F
    G810S
    D770_N771 insNPG
    20
    Exons 18–24
    T790M
    N826S
    L838VT847I
    I853TA859T
    E866K
    L833VH835L
    H850NV851X
    G863DA864T
    21
    L858R
    Exons 25–28
    L861X
    Riely, Clin Cancer Res 2006
  • 28. First line EFGR TKI or chemotherapy for non-squamous cell lung cancer harboring activating EGFR mutation
  • 29. IPASS: Objective RR in EGFR mutation positive and negative patients
    Overallresponserate (%)
    Gefitinib
    Carboplatin / paclitaxel
    EGFR M+ odds ratio (95% CI) = 2.75(1.65, 4.60), p=0.0001
    EGFR M- odds ratio (95% CI) = 0.04(0.01, 0.27), p=0.0013
    71.2%
    47.3%
    23.5%
    1.1%
    (n=132)
    (n=129)
    (n=91)
    (n=85)
    Odds ratio >1 implies greater chance of response on gefitinib
    Mok, ESMO 2008; NEJM 2009
  • 30. Improvement of lung cancer symptoms
    Adapted from Mok, NEJM 2009; supplementary appendix
  • 31. Mean change from baseline in LCS by EGFR mutation status (EFQ)
    10
    8
    EGFR M+
    Gefitinib (n=131)Carboplatin / paclitaxel (n=128)
    6
    4
    Change from baseline
    2
    0
    -2
    -4
    -6
    57
    0
    3
    6
    9
    12
    15
    18
    24
    30
    36
    42
    48
    54
    10
    8
    6
    EGFR M-
    Gefitinib (n=89)Carboplatin / paclitaxel (n=80)
    4
    2
    0
    Change from baseline
    -2
    -4
    -6
    -8
    -10
    3
    6
    9
    12
    15
    18
    24
    30
    0
    21
    27
    33
    Week
    White dotted line indicates baseline; Purple dotted lines indicate a clinically meaningful change from baseline in LCS; Mean change from baseline by EGFR mutation status was calculated post hoc; Error bars are the 95% CI of the mean; N = number of evaluable patients at baseline; Data after Week 54 (EGFR M+) and Week 30 (EGFR M-) not presented as n<20;
  • 32. IPASS: Overall survivalin EGFR mutation positive and negative patients
    EGFR mutation +
    EGFR mutation -
    Gefitinib (n=91)Carboplatin /paclitaxel(n=85)
    HR (95% CI) 1.18 (0.86, 1.63); p=0.309No. events G 82 (90%)C / P 74 (87%)Median OS G 11.2 monthsC / P 12.7 months
    Gefitinib (n=132)Carboplatin /paclitaxel(n=129)
    HR (95% CI) 1.00 (0.76, 1.33); p=0.990No. events G 104 (79%)C / P 95 (74%)Median OS G 21.6 monthsC / P 21.9 months
    1.0
    1.0
    0.8
    0.8
    0.6
    0.6
    0.4
    0.4
    Probability of survival
    Probability of survival
    0.2
    0.2
    0.0
    0.0
    52
    52
    0
    4
    8
    12
    16
    20
    44
    24
    28
    32
    36
    40
    48
    0
    4
    8
    12
    16
    20
    44
    24
    28
    32
    36
    40
    48
    Patients at risk:
    Gefitinib
    C / P
    Time from randomisation (months)
    Time from randomisation (months)
    132
    129
    126
    123
    103
    95
    70
    68
    24
    26
    11
    15
    121
    112
    88
    80
    58
    55
    46
    48
    38
    40
    6
    7
    3
    0
    0
    0
    5
    1
    69
    76
    52
    57
    40
    44
    29
    33
    26
    25
    1
    1
    19
    19
    16
    16
    11
    11
    8
    3
    0
    1
    91
    85
    0
    0
    Cox analysis with covariates; a hazard ratio <1 implies a lower risk of death on gefitinib No formal adjustment for multiple testing was made, therefore statistical significance at the traditional 5% level cannot be claimed
    Yang, ESMO 2010
  • 33. Gefitiniborcarboplatin/paclitaxelfor NSCLC withmutated EGFR
    2-year survival rate
    Gefitinib 61.4%
    Carbo/Pacli 46.7%
    Gefitinib Carbo/Pacli
    (n=114) (n=114)
    Median survival 30.5 m23.6 m
    P value =0.31
    Maemondo, NEJM 2010
  • 34. First line erlotinib in patients with (activating) EGFR mutations
    2105 pt screened for mutations (non-squamous cell)
    350 (16.6%) had mutations
    Current smoker 5.8%
    Former smoker 9.5%
    Non-smoker 37.7%
    217 ptstreated
    RR 71%
    Median PFS 14 months
    Median survival 27 months
    Rosell, NEJM 2009
  • 35. Case 1: Second line treatment with EGFR TKI
    July 10
    March 10
    July 10
  • 36. Case 1: Re-treatment with EGFR TKI atreduced dose andshort-term prednison
    February 11
    August 10
  • 37. Presence of EGFR mutations an imperfect predictor of outcometo EGFR TKIs
    PFS 27 months in patients with low BRCA1 mRNA levels, 18 months in those with intermediate levels, 10 months in those with high levels:
    Randomized phase I/II study with gefitinib and olaparibstratified for BCCA1 mRNA (SLCG)
    Rosell, CCR 2011
  • 38. Presence of EGFR mutations an imperfect predictor of outcometo EGFR TKIs
    EGFR T790Mmutation before therapy in 35%. Shorter PFS (8 vs 18 ms):
    Stratified phase II study with erl/bev (SLCG/ETOP)
    ?Irreversible TKIs (PF299, afatinib)
    Rosell, CCR 2011
    Naumov, CCR 2009
  • 39. Findings associated with resistance to EGFR TKI
    T790M mutation: 50% of tissue samples from patients with acquired gefitinib resistance and a proportion of patients at diagnosisKosaka, Clin Cancer Res 2006
    ?Irreversible TKIs (PF299, afatinib)
    MET amplification of : 22% of patients with acquiredTKI resistance: Engelman, Science 2007
    ? Combination of TKI and met inhibitor
  • 40. LUX-lung 1: afatinib (irreversible HER2 and EGFR inhibition) vs placebo
    • Adenocarcinoma of the lung, stage IIIB/IV, ECOG 0–2
    • 41. Progression after one or two lines of chemotherapy (incl. one platinum- based regimen) and ≥12 weeks of treatment with erlotinib or gefitinib
    Miller, ESMO 2010
  • 42. MET and ALK in lung cancer
    Pao & Girard, Lancet Oncol, 2011
  • 43. 43|
    Clinical trials and translational research in lung cancer: The advances over the last years
    Advanced adenocarcinoma: Molecular determinants
    • BRAF mutation
    • 44. HER2 mutation
    ETOP | EMCTO | Lugano, February 24, 2011
  • 45. 44|
    Clinical trials and translational research in lung cancer: The advances over the last years
    Advanced squamous cell carcinoma: Molecular determinants
    ETOP | EMCTO | Lugano, February 24, 2011
  • 46. 45|
    Clinical trials and translational research in lung cancer: The advances over the last years
    All histologies:
    EGFR antibody in EGFR high expressing tumors
    ETOP | EMCTO | Lugano, February 24, 2011
  • 47. 46|
    Molecular based clinical trials in lung cancer: Issues
    Molecular pathology both at diagnosis and at relapse for definition or stratification of study population mandatory
    Centralized analysis or standardization of methodologies between sites
    Availability of integrated services at sites
    Rarity of molecular subgroups
    Large networks of sites necessary to detect eligible patients
    Optimal number or sites for a given trial
    Emphasis on early decision in molecularly-driven trials
    New models of collaboration with diagnostic and pharmaceutical companies
    ETOP | Milano, February 2, 2011
  • 48. The European Thoracic Oncology Platform
    Ermatingn, April 6, 2011
  • 49. 48|
    Specific aims of ETOP according to bylaws
    To serve as a meeting platform for European study groups and institutions dealing with thoracic malignancies
    To foster intergroup studies among, but not exclusively, European study groups and institutions
    To sponsor and/or perform own studies
    To foster scientific exchange on laboratory and clinical issues among interested parties and beyond
    To provide knowledge to partners in the field
    ETOP | Ermatingen, April 6,, 2011
  • 50. Participating groups
    and institutions
    Austria
    • CECOG – Central European Cooperative Oncology Group
    Belgium
    • ELCWP – European Lung Cancer Working Party
    • 51. EORTC Lung Cancer
    • 52. Leuven Lung Cancer Group
    • 53. TOGA – Thoracale Oncologie Groep Antwerpen
    Czech Republic
    • Czech Lung Cancer Cooperative Group
    Denmark
    • DLCG – Danish Lung Cancer Group
    • 54. DOLG – Danish Oncological Lungcancer Group
    France
    • GFPC – Groupe Français de Pneumo-Cancérologie
    • 55. IFCT – Intergroupe francophone de Cancérologie thoracique
    • 56. IGR – Institut Gustave Roussy
    Germany
    • AOT – Arbeitsgemeinschaft Onkologische Thoraxchirurgie
    • 57. Arbeitsgruppe Thorakale Onkologie der Arbeitsgemeinschaft Internistische Onkologie der Deutschen Krebsgesellschaft
    • 58. Lung Cancer Group Cologne
    Greece
    • HeCOG – Hellenic Co-operative Oncology Group
    • 59. HORG – Hellenic Oncology Research Group
    Hungary
    • Thoracic Oncology Program
    Italy
    • AIOT – Associazione Italiana di Oncologia Toracica
    Poland
    • Polish Lung Cancer Group
    • 60. Medical University of Gdansk TOP Group
    Portugal
    • GECP – Grupo de estudos do cancro do pulmão
    Spain
    • SLCG – Spanish Lung Cancer Group
    Sweden
    • Swedish Lung Cancer Study Group
    Switzerland
    • SAKK – Schweizerische Arbeitsgemeinschaft fuer Klinische Krebsforschung
    The Netherlands
    • NVALT – Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose
    • 61. ROTS – Rotterdam Thoracic Oncology Study Group
    United Kingdom/Ireland
    • Birmingham Group
    • 62. BTOG – British Thoracic Oncology Group
    • 63. London Lung Cancer Group
    • 64. Manchester Lung Cancer Group
    • 65. National Cancer Research Institute – Lung Cancer Clinical Study Group
  • About LUNGSCAPE
    The LUNGSCAPE addresses the challenges of studying the molecular epidemiology of lung cancer
    by coordinating and harmonizing the procedures of of lung cancer specialists working in translational research across Europe
    by facilitating analysis of larger series of cases.
    This will:
    Expedite knowledge of the prevalence and context of current and emerging molecular biomarkers
    Facilitate more rapid translation of biomarker knowledge to the clinic
    Provide a platform for marker-driven trials of novel therapeutics.
    50|
    ETOP | LUNGSCAPE | Milano, February 2, 2011
  • 66. 51|
    Stepwise evolution
    Step 1: Retrospective analysis of 1500 completely resected NSCLC from a limited number of 7-10 sites: Mutation testing, immunohistochemistry, selected FISH on formalin-fixed, paraffin-embedded tumor tissue
    Step 2: Expansion to biopsies from advanced disease and a phased approach increasing to the number of participating sites with the aim to have participation from at least one site from all countries represented in ETOP
    Further steps and issues under considerations:Enlargement of biobank, exon sequencing (selected frozen tissue), circulating biomarkers, technology platforms, resource utilization and health economics research
    ETOP | LUNGSCAPE | Milano, February 2, 2011
  • 67. 5. Considerations for second line
    • Patients with activating EGFR mutation:
    • 68. If EGFR TKI in first line, second line platin-based combination (first line chemotherapy)
    • 69. If not in first line, now EGFR TKI
    • 70. Patients with EML4-Alk fusion gene
    • 71. Crizotinib
    • 72. EGFR WT or n/a
    • 73. Choice is between second line chemotherapy with docetaxel, for non-squamous disease pemetrexed, if not used first line, or erlotinib
  • 6. Adjuvant systemic therapy in NSCLC
    Postoperative chemotherapy with cisplatin-based combination has become standard for resected stage II and III NSCLC
    Suggestion of benefit in stage IB >4 cm
    Many open questions remain
    Is there a preferable chemotherapy regimen?
    Targeted therapy?
    How to improve efficiency?
    Integration of radiotherapy?
    Adjuvant or neoadjuvant?
    How to integrate tumor characteristics? (histology, molecular features, metabolic imaging)
  • 74. Lung Adjuvant Cisplatin Evaluation Chemotherapy vs control
    No.
    Deaths
    Hazard ratio
    No.
    Deaths
    Hazard ratio
    Category
    HR
    [95% CI]
    Category
    HR
    [95% CI]
    (Chemotherapy / Control)
    (Chemotherapy / Control)
    / No.
    Entered
    / No.
    Entered
    Stage IA
    102 / 347
    1.41
    [0.96;2.09]
    Stage IA
    102 / 347
    1.41
    [0.96;2.09]
    Stage IB
    509 / 1371
    0.92
    [0.78;1.10]
    Stage IB
    509 / 1371
    0.92
    [0.78;1.10]
    Stage II
    880 / 1616
    Stage II
    880 / 1616
    0.83
    [0.73;0.95]
    0.83
    [0.73;0.95]
    Stage III
    865 / 1247
    0.83
    [0.73;0.95]
    Stage III
    865 / 1247
    0.83
    [0.73;0.95]
    0.5
    1.0
    1.5
    2.0
    2.5
    0.5
    1.0
    1.5
    2.0
    2.5
    |
    |
    Chemotherapy
    better
    Control
    better
    Chemotherapy
    better
    Control
    better
    Test for trend: p = 0.051
    Test for trend: p = 0.051
    CT may be detrimental for stage IA, but stage IA patients were generally not given the potentially best combination cisplatin+vinorelbine (13% of stage IA patients versus ~43% for other stages)
    Pignon, ASCO 2006, JCO 2008
  • 75. Adjuvant gefitinib in unselected NSCLC
    After “curative chemoradiotherapyfor stage III:
    After curative resection:
    Kelly, JCO 2008
    Goss, ASCO 2010
  • 76. Stage IB with tumor size over 4 cm
    CALGB 9633: adjuvant carboplatin/paclitaxel in stage IB
    Adjuvant cisplatin and vinorelbinein stage I and II NSCLC: JBR.10 update
    Strauss, JCO 2008
    Butts, JCO 2010
  • 77. Adjuvant chemotherapy long term update
    Arriagada, JCO 2010
    Butts, JCO 2010
  • 78. ETOP | European Thoracic Oncology Platform | c/o IBCSG | Effingerstrasse 40 | 3008 Bern | www.etop.ch
    Visit us at www.etop.ch