Sutent Approved for GIST

[Guest guest]

Hi all,

The drug Sunitinib has just received FDA approval for the treatment of

GIST. The only other treatment (except surgery) for GIST has been

Gleevec.

For those GIST patients who fail Gleevec treatment, these patients now

have an alternative treatment with the Pfizer drug.

The CML community is anxiously awaiting approval of Disatinib as an

alternative drug to Gleevec.

Zavie

http://www.upi.com/HealthBusiness/view.php?StoryID=20060126-023050-9656r

http://www.fda.gov/bbs/topics/news/2006/NEW01302.html

EMBARGOED until Thursday, January 26, 2006, 7:30 AM (PST)

ORAL PRESENTATION

Thursday, January 26, 1:00 PM (PST)

Lead Author: D. Demetri, MD, Dana-Farber Cancer Institute

Sunitinib Is Effective in Patients with GIST that Is Resistant to

Imatinib; First Molecularly-Targeted Therapy to Prove Effective After

Another Targeted Therapy Has Failed

The detailed findings of a randomized, phase III clinical trial show

that giving the oral molecularly-targeted drug sunitinib to patients

with GIST that have continued to progress despite treatment with

imatinib can shrink tumors, slow cancer growth, and prolong lives for

these patients.

GIST, a type of sarcoma, is an uncommon form of cancer that occurs in

the abdominal organs. Although imatinib is highly effective in the

initial treatment of GIST, more than half of patients develop resistance

to this standard therapy after about two years. Sunitinib, a capsule

that is taken orally once a day, inhibits several kinase enzymes in

cancer cells. These enzymes are responsible for cellular ¡°command and

control¡± and play a crucial role in the uncontrolled growth of tumors

and the development of blood vessels that feed them.

¡°Sunitinib is the first molecularly-targeted therapy proven to work

against a cancer after another targeted therapy has failed, and this

study is highly significant because of the benefits of tumor control and

improved survival seen for patients on this drug,¡± said lead author

D. Demetri, MD, Director of the Center for Sarcoma and Bone

Oncology at Dana-Farber Cancer Institute and Associate Professor of

Medicine at Harvard Medical School. ¡°Although GIST is uncommon, the

degree to which it is understood at a molecular level, down to specific

mutations in the DNA, has made this disease a proving ground for new

therapies that could be useful in the treatment of other cancers.¡±

In the study, researchers compared overall survival and the time it took

for a patient¡¯s cancer to grow (time to progression) between two groups

of imatinib-resistant GIST patients: 207 patients received sunitinib and

105 patients received a placebo. In this trial, patients received a

placebo since there is no standard therapy known to be effective once

imatinib fails in this disease.

Time to progression was more than four times longer in the sunitinib

group (27.3 weeks) compared with the placebo group (6.4 weeks).

Sunitinib significantly reduced the risk of death by more than 50%

compared with the control group. The benefits of sunitinib were

demonstrated regardless of the dose or treatment duration of imatinib

that patients had previously received. The study results were

significantly different¡ªeven at the first interim analysis¡ªthat the

independent data monitoring committee recommended that patients

initially randomized to the control group be allowed to switch over to

take sunitinib.

Sunitinib was also generally well tolerated, with side effects such as

mild to moderate fatigue, diarrhea, nausea, mouth sores, and skin

discoloration, which rarely interfered with the ability of patients to

continue taking the drug.

Abstract #8

Improved survival and sustained clinical benefit with SU11248 (SU) in

pts with GIST after failure of imatinib mesylate (IM) therapy in a phase

III trial G. Demetri, A. T. van Oosterom, C. Garrett, M. Blackstein, M.

Shah, J. J. Verweij, G. McArthur, I. Judson, C. Baum, P. Casali

Background: SU is an oral multitargeted tyrosine kinase inhibitor with

antiangiogenic and antitumor activities that selectively inhibits KIT,

VEGFRs, PDGFR, RET and FLT3. This double-blind, placebo-controlled,

international, multicenter, phase III trial assessed the efficacy and

safety of SU in pts with progressive metastatic and/or unresectable

GIST, resistant

(-R) to, or intolerant (-I) of, prior IM therapy. Pts and methods: Pts

with documented progression of GIST despite prior IM were randomized

(2:1) to receive SU (n=207) or placebo (n=105). The starting dose was SU

50 mg given once daily for 4 weeks, followed by 2 weeks off treatment,

in repetitive 6-week cycles. Time to progression (TTP) was the primary

study endpoint with overall survival (OS) among the secondary endpoints.

Results: A prospectively planned interim analysis demonstrated strongly

positive efficacy results, which led to unblinding of the study and

crossover of all pts to open-label SU. SU improved TTP >4-fold compared

with placebo (median

TTP: 27.3 weeks vs. 6.4 weeks, P<0.0001). proportional hazard

analysis showed that all pt subgroups analyzed (including age

Conclusions: In this phase III trial of IM-R or IM-I GIST pts, treatment

with SU produced significant, sustained clinical benefit with acceptable

tolerability. Meaningful clinical activity was observed in IM-I pts,

indicating that SU may offer benefit to these pts, as well as those with

IM-R disease.

________________________________________________________________________

_______