Info
Imatinib Mesylate
- Inhibitor of KIT RTK; blocks ATP-binding
- Multiple Phase II/III clinical trials shown benefit. Overall, KIT exon 11 > exon 9 > exon 13 or 17 mts. SDH deficient GIST is → generally more resistant to TKIs
- Key trials of imatinib dosing in adv/met GIST:
- RCT of 400 mg QD vs. 600 mg QD imatinib; ORR in all pts >50%, no Δ PFS/OS (NEJM 2002;347:472)
- RCT of 400 mg QD (low dose) vs. 400 mg BID (high dose) imatinib; ORR & OS equivalent; ↑ tox but ↑ PFS w/ high dose (Lancet 2004;364:1127)
- RCT of low-dose vs. high-dose imatinib; median OS 51-55 mos; no Δ ORR/PFS/OS between groups; after POD, pts who cross over to high dose had 33% ORR or SD (JCO 2008;26:626)
- Standard therefore is → imatinib 400 mg QD for adv/met GIST; consider ↑ to high dose in exon 9 mts; PDGFR-α D842V insensitive to imatinib-consider avaprinitib (see below)
- S/e: Fluid retention, fatigue, GI, myalgia, rash, cytopenias, rare transaminitis