GIST

Question 1

Imatinib for stage IV GIST

What is response rate and median survival

Answer 1

80% of patients respond
Overall survival is nearly 60 months.

[Dematteo Lancet 2009]

Question 2

Imatinib for GIST
best prognosis mutation
worst prognosis mutation

Answer 2

best PFS with exon 11
worst PFS with exon 9

[Dematteo Lancet 2009]

Question 3

Imatinib for GIST
Median time to tumor progression
most common mechanism of resistance

Answer 3

18-24 months PFS

Resistance develops due to additional mutations in cKIT.

Resitance is sometimes overcome by increasing Imatinib or Sunitinib dose.

[Dematteo Lancet 2009]

Question 4

Imatinib for GIST

Is there a difference between 400mg v 800mg dosing?

Answer 4

In a metanalysis there is no difference in OS but a small difference in PFS.

800mg may be more effective for patients with the poor prognosis exon 9 mutation in cKIT.

[Van Glabekke Proc Am Soc Clin Oncol 2007]

Question 5

Imatinib for Adjuvant GIST - one v three years?

Answer 5

3 better than 1 and optimal duration is likely longer, but not yet defined.

SSG-18 - scandanavian sarcoma group Jama 2012

Question 6

What is natural history of a GIST <2cm?

Answer 6

NCCN and ESMO unclear and some are following or removing endoscopically. Non-surgical management is done in Europe.

Question 7

ACOSOG Z9001 (GIST trial)

Answer 7

Imatinib 800mg po daily for exon 9 KIT mutations

Question 8

Palliative treatments for bleeding GIST?

Answer 8

Surgery first-line; but there is evidence for Imatinib alone in frail patients.

Question 9

Duration of Imatinib after pre-op therapy?

Answer 9

Would generally continue for a total of at least 3 years of therapy.

Question 10

Management of rectal GIST?

Answer 10

Difficulty of surgery and high frequency of Exon 11 mutation highly favors a neoadjuvant approach.

Question 11

GIST: Imatinib resistant mutations?

Answer 11

PDGFRA exon 18 D842V mutations,
succinate dehydrogenase [SDH]
, neurofibromatosis [NF]-related GIST