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NSCLC

NSCLC. Elshami M. Elamin, MD Medical oncologist central care cancer center www.cccancer.com wichita , ks - usa. NSCLC. 85% of lung cancers Non- squamous Adenocarcinoma (subtypes based on gene expression) Broncioid (associated with increased survival in early stage)

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NSCLC

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  1. NSCLC Elshami M. Elamin, MDMedical oncologistcentral care cancer centerwww.cccancer.comwichita, ks - usa

  2. NSCLC • 85% of lung cancers • Non-squamous • Adenocarcinoma (subtypes based on gene expression) • Broncioid (associated with increased survival in early stage) • Squamoid (associated with increased survival in advanced disease) • Bronchioloalveolar is subtype of adenocarcinoma • Large-cell • Squamous

  3. Mediastinal L.N. • CT scan: • Negative LN by CT • 3% +ve by biopsy  May proceed with surgery • 1-2cm LN by CT • 10-20% +ve by biopsy • >2cm LN by CT • 60% +ve by biopsy • >4cm LN • 90% +ve by biopsy • PET scan: • 94% sensit, 86% specif, 88% accuracy • Does not replace Mediastinoscopy Mediastinoscopy + Biopsy

  4. New TNM Staging • International Association of the Study of lung Cancer (IASLC) staging is adopted by AJCC (7th edition)

  5. Changes To TNM staging • T4 pleural and/or pericardial effusion and/or pleural nodules becomes M1a • Additional nodules in the contralateral lung are subclassified as M1a • Distant metastases are subclassified as M1b

  6. Sub-classify • T1 into T1a and T1ba. T1a < 2 cmb. T1b > 2 cm and < 3 cm • T2 into T2a and T2ba. T2a > 3 cm and < 5 cmb. T2b > 5 cm and < 7 cm

  7. Reclassify • T2 lesions larger than 7 cm as T3 • T4 tumors with additional nodules in the primary lobe as T3 • M1 by additional nodules in the ipsilateral lung (different lobe) as T4

  8. *Red color indicates the changes

  9. Stages at diagnosis • 16% = localized • 5YS = 49.5% • 25% = regional LN and locally advanced • 5YS = 20.6% • 51% = metastatic • 5YS = 2.8% • 8% = unkown • 5YS = 8.3%

  10. Prognostic and Predictive Biomarkers • Prognostic: • Indicative of survival independent of therapy • Indicates innate tumor aggressiveness • ERCC1 (high expression = better prognosis) • K-ras mutation = poor prognosis • RRM1 (high expression = better prognosis) • Predictive: • Indicative of therapeutic efficaciy • EGFR mutation (E19del, L858R) = response to EGFR TKI • ERCC1 (high expression = poor response to platinum) • K-ras mutation = lack of benefit from EGFR TKI and platinum/vinorelbine • RRM1 (high expression = poor eresponse to Gemzar)

  11. treatment

  12. TREATMENT • Surgery • Lobectomy is preferred over pneumonectomy • Any surgical resection is preferred over ablation • Radiation Therapy • Chemotherapy

  13. SURGERY

  14. Surgery • Lobectomy is preferred over pneumonectomy • Any surgical resection is preferred over ablation

  15. Segmentectomy (preferred) or Wedge Resection • Not good surgical candidates • Peripheral nodule < 2cm with at least one of the following • Pure BAC histology • > 50% ground glass appearance on CT • Doubling time > 400 days

  16. Video-Assisted Thoracotomy (VAT) • Advantages: • Minimal acute/chronic pain • Shorter hospitalization • Low postop morbidity, mortality • Minimal risk of intraop bleeding • Minimal locoregional recurrence

  17. Mediastinal LND • ACOSOG Z0030 (ongoing) • N0 – N1 disease: • Med LN sampling vs complete Lymphadenctomy • Minimum of three N2 stations sampled

  18. Radiation Therapy

  19. Radiation Therapy • Adjuvant • Primary local treatment • Medically inoperable • Unresectable • Palliative

  20. Stereotactic Body RT • Inoperable stage I, N-ve, peripheral lesions <5cm • Provides statistically sig higher 5YS than 3-D RT in stage I • Limited lung mets • Brain mets

  21. Radiofrequency Ablation (RFA) • N-ve, isolated peripheral lesion <3cm: • Pt refuse surgery • Medically not fit for surgery • Previously irradiated tissue • palliation

  22. PCI (25 Gy in 10 factions) • Controversial • RTOG 0214 (PCI in stage III): • Brain mets 18% vs 7.7% • No survival benefits

  23. ADJUVANT CHEMOTHERAPY

  24. Surgery  Chemotherapy • International Adj Lung Cancer Trial (IALT): • Resected I, II, III (1867 pts) • AdjCisplatin-based chemo vs observation • 5Y f/u: • 44.5 vs 40.4% (p<0.03) • DFS 39.4 vs 34.3% (P<0.003) • 7.5Y f/u: • More death in the chemo arm • Chemo benefit is decreasing over time

  25. Surgery  Chemotherapy • NCIC CTG JBR 10 trail: • Stage IB-II (482 pts) • Vinorelbine/Cisvs Observation • OS: 94 m vs 73 m • RFS: not reached vs 46.7m • 5YS: 69 vs 54% (p=0.03) • 9Y f/u: • Chemo benefits stage II but not IB • Stage II: MS 6.8 vs 3.6 yrs • No increase in death rate

  26. Surgery  Chemotherapy • ANITA (AdjNavelbine International Trialist Association) trial: • Stage IB, II, IIIA (840 pts) • Vinorelbine/Cisvs Observation • 76m f/u: MS 65.7 vs 43.7m • Adj chemo improved 5YS in stage II-IIIA • No benefit in stage I

  27. Surgery  Chemotherapy 4. CALGB 9633 • Stage IB (344 pts) • Paclitaxel/Carbovs Observation • 3Y OS: 79 vs 70 (P=0.45) • 4Y OS: No diff • Subset analysis: Benefit tumor >4cm

  28. Surgery  Chemotherapy Summary • Meta-analysis in 4,584 pts (the Lung AdjCisplatin Evaluation) • PostopCis-based adj increased survival over 5Y • Absolute benefit 5.4% • No diff among regimens (Vinorelbine, VP, others) • Benefit greater in stage II-III and good PS • Paclitaxel/Carbo if pt cannot tolerates Cisplatin

  29. ChemoRadiation

  30. Stage IIIA What is the best?!?!?!?

  31. Unresectable IIIA/IIIB • ChemoRT is superior to RT alone • Concurrent chemoRT • Superior to Sequential • Higher rate of G3-4 esophagitis • Initial concurrent chemoRT: • Cis/VP (preferred) • Cis/Vinorelbine (preferred) • Taxol/Carbo (category 2B)

  32. Unresectable IIIA/IIIB • Phase II SWOG 9504 (83 pts stage IIIB): • Concurrent Cis/VP+RT  Doce • MS: 26m • 5YS: 29% • Phase III, stage III: • Concurrent Cis/VP+RT  Doce • No survival benefit • Increased toxicity • Randomized trial, IIIA/IIIB (203pts): • Induction chemo  RT+/-taxol • MS: 18.7 vs 14.1m (P=0.091)

  33. Resected tumor, pN2 • NCCN: • Negative margins: • Sequential Chemo  RT • Positive margins: • Postop concurrent ChemoRT +/- chemo

  34. Palliative chemotherapy

  35. Chemotherapy • Stage IV • Good PS • Platinum-based  30-40% 1 Yr survival rates • Doublets superior to single agents

  36. ROLE of chemotherapy • No chemotherapy: • 10% 1YS, 0% 2YS • Active single agent: • 15%RR, 20%1YS, 10%2YS • Active 2 drugs: • 25%RR, 35%1YS, 20%2YS

  37. Doublets chemo regimens • Cisplatin or Carbo + Taxol • Cisplatin + Vinorelbine • Cisplatin + Gemzar • Cisplatin + Pemetrexed • Cisplatin + docetaxel • Phase III studies: • Similar objective responses and Survival • They differ in Toxicities, Convenience, and Cost • Other options: • Docetaxel+ Gemzar • Gemzar+ Vinorelbine • Cisplatin + Gemzar • Carboplatin + Pemetrexed • Carboplatin + docetaxel

  38. Abraxane (Albumin-bound Taxol) • For patients with hypersensitivity reaction to: • Taxol • Docetaxel • Or if premedications are contraindicated

  39. Targeted Therapies • Anti-VEGF • Monoclonal antibody: Bevacizumab (Avastin) • Anti-EGFR • Small molecule: Erltinib (Tarceva) • Monoclonal antibody: Cetuximab (Erbitux) • Anti-Alk • Small molecule: Crizotinib (Xalkori)

  40. Anti-VEGF • Monoclonal antibody: Bevacizumab (Avastin • Unresectable, recurrent, met NON-SQUAMOUS • ECOG 4599: Avastin + Taxol + Carboplatin

  41. Anti-EGFR (TKIs) • Small molecule: Erltinib (Tarceva) or Gefitinib • Locally advanced, met NSCLC • After failure of at least one regimen • First-line if EGFR mutation present • Based on Iressa Pan Asia Study (IPASS)

  42. Iressa Pan-Asia Study (IPASS) • First-line gefitinibvs chemotherapy in clinically selected patients with EGFR mutation • Sig clinical PFS benefit • No sig OS benefit • Because there was a high rate of cross-over

  43. Anti-EGFR • Monoclonal antibody: Cetuximab (Erbitux) • Phase III FELX (Cis/Vin +/- Erbitux) • Slight OS benefit (11.3 vs 10.1m) • Toxic regimen

  44. Anti-Alk (Anaplastic Lymphoma Kinase) • Small molecule: Crizotinib (Xalkori) • Phase II: • Advanced progressive NSCLC • >80% RR • Improved pain, dyspnea, cough

  45. Maintenance therapy

  46. Definition Treatment beyond 4-6 cycles of 1st line chemotherapy in the absence of disease progression. • Selection of drug depends on histology and pt P.S.

  47. CONCEPT OF MAINTENANCE

  48. TYPES OF MAINTENANCE THERAPY • Continuation Maintenance: • Continuing 1st line cheotherapy • For a limited number of cycles • Until progression or toxicity • No randomized trial supporting continuation of cytotoxic drugs • Continuing the non-platinum drug • Gemzar • Pemetrexed • Non-squamous, EGFR mutation negative or unknown • Continuing the same targeted therapy • Bevacizumab(FDA appoved) • Cetuximab • Non-squamous, EGFR mutation negative or unknown

  49. TYPES OF MAINTENANCE THERAPY • Switch Maintenance: • Switching to a different drug • Pemetrexed(FDA approved) • Targeted: Erlotinib(FDA approved), Gefitinib • Cytotoxic: Vinorelbine, • Adding a second targeted agent after chemo • Erlotinib to Bevacizumab

  50. TARCEVA: maintenanceSATURN (Sequential Tarceva in Unresectable NSCLC) • Have two co primary end points: • PFS in the entire intent-to-treat population • PFS in pts with EGFR-positive tumors on the basis of IHC • It was large and well powered, • It was placebo controlled, following 1st line platinum-based • It met both of its primary end points with: • Significant prolongation of PFS in the intent-to-treat and the EGFR IHC-positive populations. • However, the median PFS prolongation for both populations was of only questionable clinical relevance (despite strong statistical significance) with only 1 month median benefit. • OS also was significantly prolonged in both populations, but once again with only modest absolute improvements.

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