(PowerPoint)

2,406 views
2,229 views

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
2,406
On SlideShare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
95
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

(PowerPoint)

  1. 1. Old dogmas, new tricks: the changing treatment of advanced non-small cell lung cancer Boone Goodgame, MD Division of Medical Oncology Washington University School of Medicine
  2. 2. Faculty Disclosures Dr Goodgame has received: - Consulting fees from Abraxis Bioscience. - Honoraria from Lilly Oncology
  3. 3. Old dogmas – Locally advanced NSCLC with pleural dissemination is considered “wet” IIIB and is treated as stage IV disease. – A platinum doublet is the standard of care for medically fit patients with advanced disease. – Distinction between histologic subtypes of NSCLC is inconsequential and has no direct bearing on therapy. – All third-generation platinum doublets are equivalent in terms of efficacy and are distinguished only by differing toxicity profiles. – There is no benefit to continuing chemotherapy beyond 4 to 6 cycles and patients should be observed until progression. – Median survival is 8 to 9 months and only very rare patients survive to two years. – Cetuximab has no role in the treatment of NSCLC.
  4. 4. New tricks – Updated staging system – IPASS trial of 1st line gefitinib – Pemetrexed in the first line setting – “Maintenance” docetaxel or pemetrexed – Cetuximab studies
  5. 5. Goldstraw P, et al. J Thorac Oncol. 2007;2:706-714. IASLC Staging Project: Proposed Changes Sixth Edition T/M and Descriptor Proposed T/M T1 (≤2 cm) T1a T1 (>2-3 cm) T1b T2 (≤5 cm) T2a T2 (>5-7 cm) T2b T2 (>7 cm) T3 T3 invasion T3 T4 (same lobe nodules) T3 T4 (extension) T4 M1 (ipsilateral lung) T4 T4 (pleural dissemination) M1a M1 (contralateral lung) M1a M1 (distant) M1b
  6. 6. IASLC Staging Project: Proposed Changes Sixth Edition T/M and Descriptor Proposed T/M T1 (≤2 cm) T1a T1 (>2-3 cm) T1b T2 (≤5 cm) T2a T2 (>5-7 cm) T2b T2 (>7 cm) T3 T3 invasion T3 T4 (same lobe nodules) T3 T4 (extension) T4 M1 (ipsilateral lung) T4 T4 (pleural dissemination) M1a M1 (contralateral lung) M1a M1 (distant) M1b Goldstraw P, et al. J Thorac Oncol. 2007;2:706-714.
  7. 7. IASLC Staging Project: AJCC 2009 Proposed T/M Stage Based on Proposed T/M Definitions N0 N1 N2 N3 T1a IA IIA IIIA IIIB T1b IA IIA IIIA IIIB T2a IB IIA IIIA IIIB T2b IIA IIB IIIA IIIB T3 IIB IIIA IIIA IIIB T3 IIB IIIA IIIA IIIB T3 IIB IIIA IIIA IIIB T4 IIIA IIIA IIIB IIIB T4 IIIA IIIA IIIB IIIB M1a IV IV IV IV M1a IV IV IV IV M1b IV IV IV IV Goldstraw P, et al. J Thorac Oncol. 2007;2:706-714.
  8. 8. IASLC Staging Project: Survival by pathologic stage OverallSurvival A = Sixth Edition TNM (Current) B = IASLC Proposal Goldstraw P, et al. J Thorac Oncol. 2007;2:706-714.
  9. 9. IPASS (Iressa Pan-Asia Study) Mok T, et al. Ann Oncol. 2008;19(suppl 8):viii1-viii4. Abstract LBA2.
  10. 10. IPASS Patients
  11. 11. IPASS Results • All patients: Gefitinib associated with increased PFS (HR=0.74; 95% CI, 0.65-0.85; P<.0001)1 Mok T, et al. Ann Oncol. 2008;19(suppl 8):viii1-viii4. Abstract LBA2.
  12. 12. IPASS bottom line – Phase III data to support empiric use of EGFR TKI’s in patients with increased likelihood of having an EGFR mutation. – In such without EGFR mutations, gefitinib was inferior to chemotherapy. – 1st line TKI should be considered in select patients. – Screening for mutations is ideal.
  13. 13. ECOG 1594: All third generation platinum doublets are equivalent Schiller JH, et al. N Engl J Med. 2002;346:92-98. 1.0 0.8 0.6 0.4 0.2 0 10 15 25 Months 0 5 20 30 Cisplatin/Paclitaxel Cisplatin/Gemcitabine Cisplatin/Docetaxel Carboplatin/Paclitaxel
  14. 14. Phase 3 Study Evaluating Cisplatin +Phase 3 Study Evaluating Cisplatin + Gemcitabine vs Cisplatin + PemetrexedGemcitabine vs Cisplatin + Pemetrexed Cisplatin 75 mg/m2 day 1 + Pemetrexed 500 mg/m2 day 1 (n=862) Randomization Factors • Stage • Performance status • Gender • Histologic vs cytologic diagnosis • History of brain metastases Cisplatin 75 mg/m2 day 1 + Gemcitabine 1250 mg/m2 days 1,8 (n=863) Vitamin B12, folate, and dexamethasone given in both arms Each cycle repeated q 3 wk up to 6 cycles Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551. R A N D O M I Z A T I O N
  15. 15. Cis + Gem vs Cis+ Pem: Overall SurvivalCis + Gem vs Cis+ Pem: Overall Survival Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551. 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 6 12 18 24 30 SurvivalProbability Survival Time, mo Median (95% CI) Cisplatin/pemetrexed 10.3 (9.8-11.2) Cisplatin/gemcitabine 10.3 (9.6-10.9) CP vs CG Adjusted HR (95% CI) 0.94 (0.84-1.05)
  16. 16. Pre-specified subset analysis by histology: overall survival Scagliotti GV, et al. J Clin Oncol. 2008;26:3543-3551. 2 year survival of 25% in adenocarcinoma treated with cis-pemetrexed
  17. 17. “Maintenance” chemotherapy after 4 – 6 cycles of a platinum doublet • Immediate vs delayed docetaxel • Pemetrexed vs best supportive care • Continuation of pemetrexed-bevacizumab after first line bevacizumab.
  18. 18. Immediate vs delayed docetaxel Fidias, et al. J Clin Oncol 27:591-598. 2009 p=0.001 p=0.085
  19. 19. Pemetrexed vs best supportive care Ciuleanu, et al. ASCO 2008
  20. 20. Continuation of pemetrexed-bevacizumab after first line bevacizumab Patel, et al. ASCO 2008
  21. 21. “Cetuximab has no role in the treatment of NSCLC” FLEX Study Cisplatin 80 mg/m2 on day 1 + Vinorelbine 25 or 30 mg/m2 on days 1 and 8 q3wk for a maximum of 6 cycles + Cetuximab 400 mg/m2 on d 1 250 mg/m2 /wk thereafter (n=557) Cisplatin 80 mg/m2 on d 1 + Vinorelbine 25 or 30 mg/m2 on d 1, 8 q3wk 3 for a maximum of 6 cycles (n=568 ) Eligible: • Stage IIIB/IV, EGFR-positive NSCLC by IHC (N=1125) Stratified by ECOG performance score 0/1 vs 2 Cetuximab Maintenance Until disease progression or unacceptable toxicity Pirker, et al. ASCO 2008
  22. 22. FLEX Study: Results Pirker, et al. ASCO 2008 PFS = 4.8 mo’s in both arms
  23. 23. Conclusions • We don’t have to say “wet IIIB” any more. • We need to know the histologic subtype to guide chemo choices and bevacizumab use. • With modern treatments, in adenocarcinoma, 25% of patients survive to two years. • “Maintenance” therapy with docetaxel or pemetrexed may be effective. • Cetuximab may not be completely ineffective.

×