GIST Exon gesteuerte Therapie adjuvant/palliativ

GIST Exon gesteuerte Therapie adjuvant/palliativ Peter Reichardt HELIOS Klinikum Bad Saarow / Sarkomzentrum Berlin-Brandenburg

Offenlegung potentieller Interessenkonflikte 1. Anstellungsverhältnis oder Führungsposition keine 2. Beratungstätigkeit Novartis, Pfizer, PharmaMar, Bayer 3. Aktienbesitz keiner 4. Honorare Novartis, Pfizer, PharmaMar 5. Finanzierung wissenschaftlicher Untersuchungen Novartis 6. Gutachtertätigkeit keine 7. Andere finanzielle Beziehungen keine

Adjuvant Imatinib Therapy for GIST: Rationale >50% risk of recurrence after resection in patients with high-risk GIST Imatinib represents effective oral therapy with a low toxicity profile and may be effective as an adjuvant to surgery in Treatment of low-volume microscopic disease Trials investigating use of imatinib in an adjuvant setting Randomized: ACOSOG Z9001 SSGXVIII EORTC 62024 Non-randomized: ACOSOG Z9000 Korean trial Chinese trial

Z9001: Recurrence-Free Survival DeMatteo et al. Lancet. 2009;373:1097-1104.

Twelve versus 36 months of adjuvant imatinib as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO) H. Joensuu, M. Eriksson, J. Hatrmann, K. Sundby Hall, J. Schutte, A. Reichardt, M. Schlemmer, E. Wardelmann, G. Ramadori, S. Al-Batran, B. E. Nilsson, O. Monge, R. Kallio, M. Sarlomo-Rikala, P. Bono, M. Leinonen, P. Hohenberger, T. Alvegard, P. Reichardt, J Clin Oncol 29: 2011 (suppl; abstr LBA1) Random Assignment 1:1 Imatinib for 12 months Follow-up Strata: 1) R0 resection, no tumor spillage 2) spillage or R1 resection Imatinib for 36 months Follow-up

Twelve versus 36 months of adjuvant imatinib as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO) H. Joensuu, M. Eriksson, J. Hatrmann, K. Sundby Hall, J. Schutte, A. Reichardt, M. Schlemmer, E. Wardelmann, G. Ramadori, S. Al-Batran, B. E. Nilsson, O. Monge, R. Kallio, M. Sarlomo-Rikala, P. Bono, M. Leinonen, P. Hohenberger, T. Alvegard, P. Reichardt, J Clin Oncol 29: 2011 (suppl; abstr LBA1) Study endpoints: Primary: recurrence-free survival (RFS) Time from randomization to GIST recurrence or death; second cancer not considered Secondary: Safety Overall survival (OS) GIST-specific survival

Twelve versus 36 months of adjuvant imatinib as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO) H. Joensuu, M. Eriksson, J. Hatrmann, K. Sundby Hall, J. Schutte, A. Reichardt, M. Schlemmer, E. Wardelmann, G. Ramadori, S. Al-Batran, B. E. Nilsson, O. Monge, R. Kallio, M. Sarlomo-Rikala, P. Bono, M. Leinonen, P. Hohenberger, T. Alvegard, P. Reichardt, J Clin Oncol 29: 2011 (suppl; abstr LBA1) Key inclusion criteria: Histologically confirmed KIT-positive GIST High risk of recurrence according to the modified Consensus Criteria: Tumor size >10 cm or Tumor mitosis count >10 /50 HPF or Size >5 cm and mitosis count >5/50 HPFs or Tumor rupture spontaneously or at surgery

Twelve versus 36 months of adjuvant imatinib as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO) H. Joensuu, M. Eriksson, J. Hatrmann, K. Sundby Hall, J. Schutte, A. Reichardt, M. Schlemmer, E. Wardelmann, G. Ramadori, S. Al-Batran, B. E. Nilsson, O. Monge, R. Kallio, M. Sarlomo-Rikala, P. Bono, M. Leinonen, P. Hohenberger, T. Alvegard, P. Reichardt, J Clin Oncol 29: 2011 (suppl; abstr LBA1) Recurrence-free survival (RFS) % 100 80 60 40 86.6% 60.1% 65.6% 47.9% 36 Months of imatinib 12 Months of imatinib 20 0 Hazard ratio 0.46 (95% CI, 0.36-0.65) P <.0001 0 1 2 3 4 5 6 7 Years since randomization

Twelve versus 36 months of adjuvant imatinib as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO) H. Joensuu, M. Eriksson, J. Hatrmann, K. Sundby Hall, J. Schutte, A. Reichardt, M. Schlemmer, E. Wardelmann, G. Ramadori, S. Al-Batran, B. E. Nilsson, O. Monge, R. Kallio, M. Sarlomo-Rikala, P. Bono, M. Leinonen, P. Hohenberger, T. Alvegard, P. Reichardt, J Clin Oncol 29: 2011 (suppl; abstr LBA1) Overall survival (ITT) % 100 80 96.3% 94.0% 92.0% 81.7% 60 40 20 0 36 Months of imatinib 12 Months of imatinib Hazard ratio 0.45 (95% CI, 0.22-0.89) P =.019 0 1 2 3 4 5 6 7 Years since randomization

Follow-up results after 9 years of the ongoing, phase II B2222 trial of imatinib mesylate in patients with metastatic or unresectable KIT+ gastrointestinal stromal tumors (GIST) M. von Mehren et al., J Clin Oncol 29: 2011 (suppl; abstr 10016)

Sorafenib Reichardt et al., J Clin Oncol 27:15s, 2009 (suppl; abstr 10564)

Sorafenib in patients with imatinib and sunitinib-resistant gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial H. L. Kindler et al., J Clin Oncol 29: 2011 (suppl; abstr 10009)

A phase II study of sorafenib in patients with metastatic or unresectable gastrointestinal stromal tumors with failure of both imatinib and sunitinib: A KGSG study M. Ryu et al., J Clin Oncol 29: 2011 (suppl; abstr 10010)

A multicenter phase II study of regorafenib in patients with advanced gastrointestinal stromal tumor (GIST), after therapy with imatinib and sunitinib S. George et al., J Clin Oncol 29: 2011 (suppl; abstr 10007)