Barry W. Feig, M.D.Robert S. Benjamin, M.D.

The SARCOMA Center

The Connective Tissue Oncology Society

Surgical Treatment of GIST post Imatinib

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0 1 2 3 4 5 6 7 8 9 10

1.00

0.80

0.60

0.40

0.20

0.00

YEARS

PROPORTION

vs

vsvs p = 0.64

p = 0.002p = 0.002

TOTAL FAIL

9326396

12376697

Chemotherapy + Surgery CRChemotherapy CRPartial ResponseStable Disease

SOFT TISSUE SARCOMAS 1971-1977SOFT TISSUE SARCOMAS 1971-1977

Time to Progression - Distant Time to Progression - Distant MetastasesMetastases

GIST: Management of Resistance

• If the majority of tumor is controlled by imatinib mesylate, then continue therapy

• Dose escalation up to 800-1000 mg/d as tolerated

• Surgical resection of progressing sites if possible

• Other trials

Demetri et al. JNCCN. 2004;21(suppl 1):S1.

RADIOGRAPHIC RESPONSE TO IMATINIB IN RECURRENT / METASTATIC GIST (N=35)

Response category

Complete resection

(n=11)

Incomplete resection

(n=24)

Complete response 0 (0%) 0 (0%)

Partial response 10 (91%) 1 (4%) Continuous regression 2 0

Initial regression then stable 8 1

Stable disease 0 (0%) 0 (0%)

Progressive disease 1 (9%) 23 (96%) Initial regression then progression 0 18

Continuous progression 1 5

TIME OF SURGERY IN IMATINIB RESPONSIVE RECURRENT / METASTATIC GIST

COMPLETE RESECTION

(N=11)

INCOMPLETE RESECTION

(N=18)

Median (months) 10.0 18.0 23.7

SURGERY

SURGERY

PROGRESSION

P=0.04

FOLLOW-UP RECURRENT / METASTATIC GIST (N=35)

Follow-up

Complete resection

(n=11)

Incomplete resection

(n=24)P

Since imatinib initiation

(months)39.1

(28.7 – 48.1)

36.2

(11.6 – 48.0)

0.10

Postoperative (months) 30.7

(0.2 - 35.3)

11.8

(0.8 – 30.9)

<0.001

GIST Surgery: Randomized Study

• Surgery vs No Surgery

• Surgery at maximum response vs Surgery at first evidence of relapse.

TIME OF SURGERY IN IMATINIB RESPONSIVE RECURRENT / METASTATIC GIST

COMPLETE RESECTION

(N=11)

INCOMPLETE RESECTION

(N=18)

Median (months) 10.0 18.0 23.7

SURGERY

SURGERY

PROGRESSION

P=0.04

TIME OF SURGERY IN IMATINIB RESPONSIVE RECURRENT / METASTATIC GIST

R

A

N

D

O

M

I

Z

E

Months (estimate) 10 18 20

EARLY SURGERY

DELAYEDSURGERY

PROGRESSION

GIST Surgery: Endpoints• Time to Progression from start of imatinib

– If no difference, then surgery does not have a role

– If TTP longer with early surgery, then surgery is adding

• Survival– If no difference, delayed surgery is preferable

(not all will need it).– If survival better with early surgery, it is better

to do at that time.

Barry W. Feig, M.D.Robert S. Benjamin, M.D.

The SARCOMA Center

The Connective Tissue Oncology Society

Surgical Treatment of GIST post Imatinib

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.