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Discussion Gastric Cancer LBA 4002, abstracts 4003, 4004

Discussion Gastric Cancer LBA 4002, abstracts 4003, 4004. Florian Lordick, MD Germany. Gastric Cancer. Lung (1.4 million deaths) Stomach (740 000 deaths) Liver (700 000 deaths) Colorectal (610 000 deaths) Breast (460 000 deaths) http://www.who.int factsheet N°297 February 2011.

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Discussion Gastric Cancer LBA 4002, abstracts 4003, 4004

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  1. Discussion Gastric CancerLBA 4002, abstracts 4003, 4004 Florian Lordick, MDGermany

  2. Gastric Cancer • Lung (1.4 million deaths) • Stomach (740 000 deaths) • Liver (700 000 deaths) • Colorectal (610 000 deaths) • Breast (460 000 deaths) http://www.who.int factsheet N°297 February 2011

  3. Yung-Jue Bang et al. LBA 4002CLASSIC – Adjuvant Chemotherapy • Asia: Korea, China, Taiwan • Surgical technique: D2 resection 8 cycles of XELOX (6 months) RANDO MIZ ATION n = 520 Surgically (D2) resected Stage II, IIIA, or IIIB*GC, 6 weeks prior to randomization No prior chemotherapy or radiotherapy Capecitabine: 1,000 mg/m2 bid, d1–14, q3w Oxaliplatin: 130 mg/m2, d1, q3w N = 1035 Observation: No adjuvant therapy n = 515 • Primary endpoint: 3-year DFS‡ • Secondary endpoints: overall survival and safety profile

  4. CLASSIC – Primary Endpoint Met(3-year DFS at Interim Analysis) 3-year DFS 1.0 74% 0.8 XELOX, n = 520 0.6 Observation, n = 515 60% 0.4 0.2 HR = 0.56 (95% CI 0.44–0.72) P < .0001 0.0 0 6 12 18 24 30 36 42 48 Time (months) No. left XELOX 520 410 333 246 166 74 30 10 443 Observation 515 414 352 286 209 147 58 22 6 ITT population Median follow-up 34.4 months (range 16–51)

  5. CLASSIC – Overall Survival Overall survival 1.0 0.8 XELOX, n = 520 0.6 Observation n = 515 0.4 0.2 HR = 0.74 (95% CI 0.53–1.03) P = .0775 0.0 0 6 12 18 24 30 36 42 48 Time (months) No. left XELOX 520 451 395 304 216 120 35 16 468 Observation 515 458 441 378 286 203 112 34 12 ITT population Median follow-up 34.4 months (range 16–51)

  6. CLASSIC – Discussion Is the positive result of CLASSIC surprising? No, it’s not!

  7. CLASSIC – Discussion ATCS-GC (Japan): S-1 vs. surgery alone Relapse-freesurvival Overall survival HR = 0.68 (95% CI, 0.52 to 0.87) P = 0.003 HR = 0.62 (95% CI, 0.50 to 0.77)P<0.001 Sakuramoto S et al. N Engl J Med 2007;357:1810-1820

  8. CLASSIC – Discussion GASTRIC Group Meta-analysis 6% differenceat 5 years HR = 0.82; p < 0.001 The Gastric Group. JAMA 2010; 303: 1729-1737

  9. CLASSIC – Discussion Are the results of CLASSIC transferable to the Western World? There are some caveats!

  10. CLASSIC – Discussion • Median age (Classic): 56 years Age-specificincidence rate forgastriccancer in German males Robert-Koch-Institute 2010

  11. CLASSIC – Discussion • Tumor location (Classic): mid & distal 78% Change ofgastriccancerepidemiologyin the Western World Devesa et al. Cancer 1998; 83: 2049-2053

  12. CLASSIC – Discussion • D2 resection(Classic):median 42 lymph nodes examined (range 9-127) US INT 0116 (SWOG 9008)Macdonald et al. 2001 D2-Resection 10% D1-Resection 36% D0-Resection 54% UK MAGICCunningham et al. 2006 D2-Resection 41% D1-Resection 19% OtherResections 40%

  13. Gastric Cancer – Discussion Doesthesurgicalapproachdeterminetheoptimal adjuvanttreatmentstrategy? Asia: Radicalresection (D2) Adjuvantchemotherapy Sub-radicalresection (≤ D 1) Adjuvantchemoradiation

  14. Charles S Fuchs et al. # 4003 CALGB 80101 – Adjuvant Chemoradiation • North America: Intergroup study R A N D O M I Z E 5-FU/LVx 1 5-FU/LVx 2 5-FU IVCI RT 5-FU IVCI RT ECFx 1 ECFx 2 N = 540Stratificationby T stage, N stage, < or ≥ 7 examinedlymphnodesPrimary endpoint: improvement in overallsurvival

  15. CALGB 80101 – Adverse Events ≥ 3

  16. CALGB 80101 – Disease-free Survival P, log rank = 0.99

  17. CALGB 80101 – Overall Survival P, log rank = 0.80

  18. CALGB 80101 – Discussion Is the result of CALGB 80101 surprising? No, it’s not surprising!

  19. CALGB 80101 – Discussion GISCADadjuvant PELF vs FU Cascinu et al. JNCI 2007; 99: 601-607

  20. CALGB 80101 – Discussion GASTRIC Group Meta-analysis The Gastric Group. JAMA 2010; 303: 1729-1737

  21. Therapy of Gastric Cancer in the U.S.

  22. CALGB 80101- Discussion • What could we make better? Radiation qualityassurance CALGB 80101 (Fuchs et al. 2011) 15% of the treatment plans were found to contain major deviations INT 0116 (Macdonald et al. 2001) 6.5% majordeviations

  23. CALGB 80101- Discussion • What could we make better? Surgicalqualityassurance CALGB 80101 (Fuchs et al. 2011) D2 LN dissection not mandated 33% pts had <15 lymph nodes examined!

  24. CALGB 80101- Discussion • Role of D2 lymph node dissection • Long-termfollow-upoftheDutch D1/D2 trial • Songun et al. Lancet Oncol2010; 11: 439-449 • ESMO Practice Guidelines • Okines et al. Ann Oncol 2010, 21 (suppl5); v50-v54 • NCCN Guidelines v 2.2011 • www.nccn.com

  25. CALGB 80101- Discussion NCCN v2.2011 guidelines: Gastricresectionshouldincludethe regional lymphatics: perigastriclymphnodes (D1) andthosealongthenamedvesselsoftheceliacaxis (D2) with a goalofexaminingat least 15 orgreaterlymphnodes. Surgicalexperience & hospitalvolumematter!

  26. Summary Adjuvant Gastric Cancer EuropePerioperativeCTx(Epirubicin)-Platin-5FU N America AdjuvantR-CTx 45 Gy + 5FU/LV AsiaAdjuvantCTx S-1 orCapox

  27. Advanced Gastric Cancer • 1st linechemotherapyprolongssurvival • 1st linechemotherapyimprovessymptomcontrol Wagner et al. J Clin Oncol2006; 24: 2903-9 Establishedstandard 1st line:Platin-fluoropyrimidine-combinationsPark et al. # 4004Is there a roleforsecond-linechemotherapy?

  28. 2nd line Chemotherapy (SLC)Park et al. #4004 Screening & consent for RCT Refused RCT, but prefer SLC Willing to participate RCT Refused RCT, but prefer BSC 2:1 randomization SLC SLC BSC BSC Docetaxel or irinotecan N = 202 RCT RCT + PPT RCT: randomized controlled trialPPT: patient-preference trial ClinicalTrials.gov,NCT00821990

  29. Survival (Park et al. #4004) 1.0 Median f/u (95% CI): 17 mo (16-18 mo) Median 95% CI 0.8 SLC + BSC 5.1 mo 4.0-6.2 BSC alone 3.8 mo 3.0-4.6 0.6 Log-rankP=0.009 Probability Survival 0.4 0.2 0.0 0 6 12 18 Months

  30. Critizism (Park et al. #4004) I missed… • Data on qualityoflife • Data on symptomimprovement / control

  31. Post progression chemotherapy German AIO Study Thuss-Patience P. Eur J Cancer; 2011; accepted for publication

  32. Park et al. #4004 Conclusion 2nd linechemotherapyhas a provenbenefit in advancedgastriccancer andshouldbeofferedtopatients withan acceptableKarnofksy PS andmotivationtoreceivefurtherchemotherapy

  33. Thank you for your kind attention… … andhave a safetriphome!

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