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Fotios Loupakis U.O. Oncologia 2 Universitaria Azienda Ospedaliero-UniversitariaPisana Pisa, ITALY

AIOM Post ASCO review Updates and news from the Annual Meeting in Chicago Bologna 19-20 Giugno 2010. COLON CANCER Wrap up. Fotios Loupakis U.O. Oncologia 2 Universitaria Azienda Ospedaliero-UniversitariaPisana Pisa, ITALY. Wrap up the Olympians: a mortal sin!.

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Fotios Loupakis U.O. Oncologia 2 Universitaria Azienda Ospedaliero-UniversitariaPisana Pisa, ITALY

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  1. AIOM Post ASCO review Updates and news from the Annual Meeting in Chicago Bologna 19-20 Giugno 2010 COLON CANCER Wrap up Fotios Loupakis U.O. Oncologia 2 Universitaria Azienda Ospedaliero-UniversitariaPisana Pisa, ITALY

  2. Wrap up the Olympians: a mortal sin!

  3. ASCO 2009…2010…201X: the Middle Ages of CRC?

  4. Waiting for the Renaissance of CRC… Asking the PAST to plan the FUTURE: (i.e.: …the optimal use of bevacizumab…) Asking the FUTURE to move from the PAST: (…new drugs for old targets, new targets for old drugs/combinations…)

  5. Chapter 1 Let’s optimize Beva!

  6. Inspired from Ellis’ talk, ASCO 2010… Is beva as maintenance enough?  MACRO (yes… or not?) Is beva as maintenance efficacious?  CAIRO-3 (awaited) Is beva post-progression efficacious?  BriTE, ARIES (suggestions) Random Prospective (awaited) Has beva left the lab for good?  Upfront predictors (difficult) Markers of acquired resistance (suggestions)

  7. The MACRO Trial ARM A: XELOX/BV until PD ARM B: XELOX/BV x6c  BV until PD Taberneroet al. ASCO ‘10

  8. Venook’s point of view (but also Di Maio’s just reading the abstract!)

  9. The CAIRO-3 Trial PFS2 PFS1 PROGRESSION PROGRESSION RANDOMIZE observation MTD chemotherapy 6 cyclesof XELOX/BV MTD chemo +Beva SD PR CR LD Cape + Beva PD not eligible

  10. Yaaaawn! Stop and go Until PD 6mos Holidays CT-freeintervals

  11. ARIES Beva beyond PD: OS HR=0.52 (95% CI: 0.42–0.63) p<0.001 Cohn et al. ASCO 2010

  12. Data from phase IV BRiTE trial BBP: 19.2 months No BBP: 9.5 months No treatment: 3.6 months HR = 0.61; P < 0.0001 (BBP vs No BBP) Grothey et al. J Clin Oncol 2009

  13. On the right track toward evidence: ongoing phase III trials Accrual completed ML18147 N=820 Recruiting BEBYP N=262 Recruiting SWOG-S0600 N=1260

  14. Predictive factors (???) Investigated determinants: • KRAS, BRAF and p53 mutational status; • P53 and thrombospondin-1 tissue expression; • VEGF epithelial and stromal expression; • Microvascular density • VEGF and VEGFR SNPs • VEGF plasma levels Ellis, ASCO 2010

  15. VEGF -1498 C/T SNP: a retrospective experience CONTROL GROUP BEVACIZUMAB GROUP -1498 T/T (N=25) median PFS: 8.6 months -1498 C/T (N=55) median PFS: 8.2 months -1498 C/C (N=27) median PFS: 8.0 months Logrank test p= 0.662 -1498 T/T (N=29) median PFS: 7.5 months -1498 C/T (N=60) median PFS: 10.5 months -1498 C/C (N=22) median PFS: 12.8 months Logrank test p= 0.0046 Loupakis et al. ESMO 2009

  16. From retrospective to prospective Ellis L, ASCO 2010 Pander J, BJC 2010 Prospective Pro.VE.TT.A. trial is currently enrolling patients

  17. ARIES Beva 2nd-Line (Beva treatedvs Beva-naive): PFS Is the term“resistance”, as we use it, valid for beva? Bekaii-Saab et al. ASCO 2010

  18. Are there biomarkers of acquired resistance? Kopetz et al. J ClinOncol 2010

  19. I love this study! Kopetz et al. ASCO 2010

  20. Other suggestions from our experience… p<0.0001 Plasma sVEGFR-2 (pg/ml) at PD p=0.083 p=0.051 Plasma sVEGFR-2 (pg/ml) at day 155 Loupakis et al. Submitted

  21. An area of excitement (Kopetz S., ASCO 2010) Kerbel, ASCO 2010 New potential“sequential” targets? Kopetz, ASCO 2010

  22. Will this field of research “re-open” momentarily closed questions? HR Wolmark et al. ASCO 2009 Time (years) Wolmark et al. ASCO 2010

  23. Fantasy? BEVACIZUMAB ALL LIFE LONG

  24. Chapter 2 BRAF: between prognosis& prediction

  25. Chapter 2 BRAF: between prognosis & prediction Richman, JCO 2009 Souglakos, BJC 2009 Koopman, ESMO 2009

  26. BRAF as extremely negative prognostic factor: no doubt! Roth, ASCO 2010

  27. BRAF & prediction Siena, et al. JNCI 2010

  28. Previously…on Crystal… OS CONCLUSION BRAF status does not appear to be a strong predictive biomarker for the addition of cetuximab to FOLFIRI in 1st-line PFS RR Van Cutsem et al. ASCO GI 2010

  29. Bokemeyeret al. What’s new adding 11 pts (5+6)? Straight from the podcast “…for all the three parameters analyzed the addition of cetuximab to chemotherapy still improves…compared to chemo-alone… although this was not statistically significant due to the low number of patients with BRAF mutation…” OS CONCLUSION Patients with BRAF mutation still seem to benefit from the addition of cetuximab to 1st-line chemotherapy. BRAF mutation status cannot be used as a relevant predictive marker for the use of cetuximab in 1st-line PFS RR Bokemeyer et al. ASCO 2010

  30. BRAF: conclusions …a riddle, wrapped in a mistery, inside an enigma …but perhaps there is a key. That key is Russian national interest! Our patients’

  31. Let’s change our way of thinking: thank you Sabine! Tejpar, ASCO 2010

  32. Things to do... Kopetz S et al. ASCO 2010

  33. Chapter 3 CONCLUSIONS …how to move forward

  34. FOLFIRINOX in Pancreatic Cancer: OS ConroyTet al. ASCO 2010

  35. FOLFOXIRI in CRC: OS 15% Median follow up: 60.6 months 8% Falcone et al. ECCO-ESMO ‘09

  36. FOLFOXIRI in Gastric Cancer (????) RESPONSE RATE: 67% Falcone et al. ECCO-ESMO ‘09

  37. Triple chemo-association in the“era of biologics”: anachronism?

  38. …and things not to do Motesanib with or without panitumumab plus FOLFIRI or FOLFOX for the treatment of Metastatic colorectal cancer Tebbutt N et al. ASCO 2010

  39. …but to improve…research should be improved!

  40. Target our drug since its birth… Pittset al.Clin Can Res ‘10

  41. fotiosloupakis@gmail.com cremolini@sssup.it

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