SlideServe
Télécharger Obtenir Pro
Menu
Accueil Pro
Préférences
ApparenceLight Aide et commentaires
© SlideServe · v2026

Optimal Duration of Adjuvant Imatinib Therapy for Resected Gastrointestinal Stromal Tumors

ervin avatar
ervin
53 diapositives · 688 Views · Jul 20, 2014

This presentation focuses on the critical findings of the SSGXVIII study comparing 12 versus 36 months of adjuvant imatinib treatment for patients with resected gastrointestinal stromal tumors (GISTs). It covers the methodology, validity of conclusions, and implications for adjuvant therapy in GIST management. Key discussions include the treatment of metastatic disease, the risks of recurrence, and considerations for prolonged therapy. The outcomes indicate that extended imatinib treatment can enhance recurrence-free survival and overall survival, raising questions about who should receive such therapy.

#optimal duration of adjuvant imatinib therapy for resected gastrointestinal stromal tumors #optimal duration of adjuvant imatinib therapy for resected gastrointestinal stromal tumors ppt #powerpoint #presentation
Optimal Duration of Adjuvant Imatinib Therapy for Resected Gastrointestinal Stromal Tumors - slide 1
01 / 53Optimal Duration of Adjuvant Imatinib Therapy for Resected Gastrointestinal Stromal Tumors
1 / 17

Télécharger la présentation

Optimal Duration of Adjuvant Imatinib Therapy for Resected Gastrointestinal Stromal Tumors
Une image / un lien ci-dessous est fourni (tel quel) pour télécharger la présentation

Politique de téléchargement : le contenu du site vous est fourni TEL QUEL pour votre information et votre usage personnel ; il ne peut être vendu, concédé sous licence ni partagé sur d’autres sites sans l’accord de son auteur.Le contenu vous est fourni TEL QUEL, pour votre information et votre usage personnel uniquement. Téléchargez la présentation en cliquant sur ce lien. Lors du téléchargement, si vous ne parvenez pas à télécharger une présentation, l’éditeur a peut-être supprimé le fichier de son serveur.Pendant le téléchargement, si vous ne parvenez pas à obtenir une présentation, le fichier a peut-être été supprimé par l’éditeur.

F I N

Plus de contenu associé

Transcription de la présentation

  1. From Here to Eternity: Optimal Duration of Post-Operative Therapy for Patients with Resected Gastrointestinal Stromal Tumors Charles D. Blanke, M.D., F.A.C.P., F.R.C.P.C. Chief, Medical Oncology, University of British Columbia Vice-President, British Columbia Cancer Agency

  2. SSGXVIII: 12 versus 36 Months of Adjuvant Imatinib in GIST • Background on treatment of GISTs • Metastatic disease • Adjuvant • SSGXVIII methodology and validity of conclusions • Questions raised by SSGXVIII • Adjuvant treatment of other tumours • Conclusions and issues outstanding

  3. April 5, 2001

  4. B2222: Imatinib Treatment of Patients with Advanced GISTs is Highly Effective von Mehren et al., Proc Am Soc Clin Oncol 2011

  5. B2222: Imatinib Treatment of Patients with Advanced GISTs is Highly Effective Are these long-term survivors cured? No!

  6. BFR14 – Study Design R A N D O M I S A T I O N PD Imatinib 400 mg STOP Advanced/ metastatic GIST CR PR SD Imatinib 400 mg Surgery possible if resectable Imatinib 400 mg Follow-up 1 / 3 / 5 years Courtesy Dr. Axel Le Cesne

  7. BFR14: Progression-Free Survival (After Responding) 1, 3 and 5 Years After Stopping Imatinib 1.0 1 year 0.9 0.8 3 years 0.7 5 years 0.6 Survival probability 0.5 0.4 0.3 0.2 0.1 0.0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 Months after randomisation to stopping Blay et al, J Clin Oncol 2007; Le Cesne et al, Lancet Oncol 2010; Ray-Coquard et al, PASCO 2010

  8. 1.0 0.9 0.8 0.7 0.6 Survival probability 0.5 0.4 0.3 0.2 0.1 0.0 0 6 12 18 24 Months from 5-year point BFR14: PFS for Continuous Group

  9. 1.0 0.9 0.8 0.7 0.6 Survival probability 0.5 0.4 0.3 0.2 0.1 0.0 0 6 12 18 24 Months from 5-year point BFR14: PFS for Continuous Group 5 years not enough to control patients with advanced GIST in complete remission… Would findings be the same in adjuvant use? Adapted Le Cesne

  10. SSGXVIII: 12 versus 36 Months of Adjuvant Imatinib in GIST • Background on treatment of GISTs • Metastatic disease • Adjuvant • SSGXVIII methodology and validity of conclusions • Questions raised by SSGXVIII • Adjuvant treatment of other tumours • Conclusions and issues outstanding

  11. Disease-Specific Survival After Surgery Alone for GIST Fraction Surviving DeMatteo et al., Ann Surg 2000

  12. Phase III Z9001 ACOSOG Adjuvant Trial Primary GIST > 3 cm Complete Gross Resection Tumor KIT + Placebo x 1 yr Imatinib x 1 yr Double-blind cross-over if recur Recurrence/Survival (6/2002 – 4/2007) Courtesy Corless and DeMatteo

  13. ACOSOG Z9001: Recurrence-Free Survival Imatinib Placebo Adapted DeMatteo et al., Lancet 373:1097, 2009

  14. Recurrence-Free Survival Curve on Z9001 Suggests Lack of Cure

  15. Z9001: Overall Survival No overall survival benefit was observed with adjuvant therapy

  16. SSGXVIII: 12 versus 36 Months of Adjuvant Imatinib in GIST • Background on treatment of GISTs • Adjuvant • Metastatic disease • SSGXVIII methodology and validity of conclusions • Questions raised by SSGXVIII • Adjuvant treatment of other tumours • Conclusions and issues outstanding

  17. SSGXVIII Study Snapshot • Key eligibility factors: • Resected KIT+ GIST • High risk for recurrence by 2002 Modified Consensus Criteria • Recurrence-free survival hazard ratio aimed for: 0.44 • Hazard ratios found: RFS = 0.46; OS = 0.45 • Authors concluded 3 years of imatinib improve RFS and OS

  18. SSGXVIII: Methodology and Validity of Conclusions Goals were reasonable Methodologies for primary and secondary objectives were sound Conclusion regarding recurrence-free survival is valid Conclusion regarding overall survival is valid, with some limitations

  19. SSGXVIII: 12 versus 36 Months of Adjuvant Imatinib in GIST • Background on treatment of GISTs • Metastatic disease • Adjuvant • SSGXVIII methodology and validity of conclusions • Questions raised by SSGXVIII • Adjuvant treatment of other tumours • Conclusions and issues outstanding

  20. SSGXVIII Question 1: Can we administer imatinib for a prolonged period in the adjuvant setting?

  21. SSGXVIII: Completion of Therapy Category 12 Months 36 Months n = 181 n = 177 On treatment at data cut-off (%) 0 11 Early discontinuation (%) 16 36 - GIST recurred on treatment 2 7 - Adverse event 8 15 - Other reason 6 14 Adapted Joensuu

  22. SSGXVIII: Completion of Therapy Category 12 Months 36 Months n = 181 n = 177 On treatment at data cut-off (%) 0 11 Early discontinuation (%) 16 36 - GIST recurred on treatment 2 7 - Adverse event 8 15 - Other reason 6 14 Adapted Joensuu

  23. Issues Related to Administering Imatinib for a Prolonged Period in the Adjuvant Setting • Grade 3/4 toxicities similar in frequency on both arms • Twice as many dropped out on 3-year arm related to an adverse event; same for “other” reasons • Were low-grade side effects challenging to tolerate long-term? • Is it too difficult to take a pill for years with no disease evident?

  24. Difficulties on the 3-year arm of SSGXVIII may bode poorly for therapy lasting even longer

  25. SSGXVIII Question 2: Who should receive adjuvant therapy after resection of GIST?

  26. Who Should Receive Post-Operative Imatinib? • SSGXVIII eligibility included being at “high risk” for recurrence • “High risk” patients have recurrence probablilities ranging from ~34% to nearly 100% • Can assign an actual number to individual patients using clinical factors and Gold nomogram1 1Gold et al., Lancet Oncol 2009

  27. Clinical Risk Factors and Risk-Reduction with 3 Years of Adjuvant Imatinib

  28. Clinical Risk Factors and Risk-Reduction with 3 Years of Adjuvant Imatinib

  29. Risk-Reduction with 3 Years of Adjuvant Imatinib (cont.) • Within categories, higher and lower risk patients enjoy the same benefits from longer therapy • We can thus apply SSGXVIII’s results to patients at roughly a 1 in 3 or greater chance or recurrence

  30. Risk-Reduction with 3 Years of Adjuvant Imatinib (cont.) • Within categories, higher and lower risk patients enjoy the same benefits from longer therapy • We can thus apply SSGXVIII’s results to patients at roughly a 1 in 3 or greater chance or recurrence • But should we?

  31. Who Should Receive Adjuvant Therapy after Resection of GIST? • In current practice, adjuvant imatinib often administered to patients with >25% chance of recurrence • Therapy routinely continued for >1 year, especially in highest-risk patients • Is 25% to ~35% reasonable, given the possibility we may need to treat very long term? • Possible strategy: Give imatinib for 3 years to lower risk patients and >3 years for higher risk • Not recommended

  32. SSGXVIII Question 3: What is the ideal duration for adjuvant GIST treatment with imatinib?

  33. SSGXVIII: Recurrence-Free Survival 100 88.1% % 36 months 80 67.4% 12 months 60 62.1% 50.3% 40 Hazard ratio 0.46 (95% CI, 0.31-0.68) P <0.0001 20 0 0 1 2 3 4 5 6 7 Years since randomization

  34. SSGXVIII: Recurrence-Free Survival 100 % 36 months 80 12 months 60 40 20 0 0 1 2 3 4 5 6 7 Years since randomization

  35. SSGXVIII: Recurrence-Free Survival 100 % 36 months 80 12 months 60 40 20 0 0 1 2 3 4 5 6 7 Years since randomization

  36. Recurrence-Free Survival Assuming Patients on Both Arms Stop Therapy at the Same Time 100 % 36 months 80 12 months 60 40 20 0 0 1 2 3 4 5 6 7 Years

  37. Is a 3-year treatment duration (versus one year) delaying recurrence 2 years longer without increasing cure rates?

  38. SSGXVIII: Overall Survival 96.3% 92.0% 100 94.0% % 80 81.7% 60 36 months Hazard ratio 0.45 (95% CI, 0.22-0.89) P = .019 12 months 40 20 0 0 1 2 3 4 5 6 7 Years since randomization

  39. SSXVIII: What Does the Overall Survival Difference Mean? • Improved long-term overall survival usually equates with increased cure rate • Do not know if overall survival difference will hold up • Period by period hazard rate assessment necessary to prove better overall survival from increased cure rate • Cure = finite drug administration; Prolonged remission = lifelong treatment

  40. What is the Ideal Duration for Imatinib in the Adjuvant Setting? • 3 years, as per the experimental arm on SSGXVIII? • 5 to 10 years, still aiming for cure? • Indefinite, abandoning goal of cure? • Combination: Finite for some, lifelong for others?

  41. Heinrich et al., J Clin Oncol. 2006 GIST Practice: Can We Use the Lab to Guide Us? GIST H and E Adapted Corless Day 0 Day 7 Duensing et al., Oncogene 2004

  42. SSGXVIII: 12 versus 36 Months of Adjuvant Imatinib in GIST • Background on treatment of GISTs • Adjuvant • Metastatic disease • SSGXVIII methodology and validity of conclusions • Questions raised by SSGXVIII • Adjuvant treatment of other tumours • Conclusions and issues outstanding

  43. Adjuvant Treatment of Other Solid Tumours 1breast cancer 2prostate cancer 3colon cancer

  44. X Adjuvant Treatment of Other Solid Tumours 1breast cancer 2prostate cancer 3colon cancer

  45. Identifying the Ideal Adjuvant Duration for Imatinib in GIST and for Other Biologics • As of June 5th, 2011, we do not know how long to administer adjuvant imatinib in GIST • We still need to test multiple possible durations • Economic and patient availability limit feasibility of doing so • Little enthusiasm for 5 year v. 10 year v. lifelong study

  46. Post-Resection Evaluation of Recurrence-Free Survival for Gastro-Intestinal Stromal Tumors Treated with Adjuvant Imatinib: PERSIST-5 Resected GIST >2 cm and mitotic rate >5 or Non-gastric primary >5 cm Imatinib 400 mg/d x 5 years Register Phase II N = 85 patients Primary objective: Recurrence-free survival Adapted DeMatteo

  47. SSGXVIII: 12 versus 36 Months of Adjuvant Imatinib in GIST • Background on treatment of GISTs • Adjuvant • Metastatic disease • SSGXVIII methodology and validity of conclusions • Questions raised by SSGXVIII • Adjuvant treatment of other tumours • Conclusions and issues outstanding

  48. My Conclusions from SSGXVIII • In GIST, 3 years of adjuvant imatinib are better than one in terms of recurrence-free and overall survival • 3 years of post-operative imatinib treatment represent the new gold standard for patients with resected “high-risk” GISTs • The overall survival advantage demonstrated means we cannot try to “catch-up” later, in advanced disease setting

  49. Issues Remaining from SSGXVIII • Should we treat post-operative patients longer than 3 years? • Should we treat lifelong? • Whom should we treat with adjuvant imatinib? • I will use a “50% chance of recurrence” threshold

  50. Issues Remaining (cont.) • How do we best study adjuvant therapy for GISTs? • Probably will not truly be able to figure out how long to treat or • Will not matter, if GISTs are incurable in any setting • Thus, need to identify biomarkers to tell us whomto treat