The Role of mTOR in Cancer Etiology and Treatment

1
The Role of mTOR in Cancer Etiology and
Treatment Based on presentations from the 44th
Annual Meeting of the American Society of
Clinical Oncology (ASCO) May 30-June 3,
2008 Chicago, Illinois
2
(No Transcript)
3
(No Transcript)
4
(No Transcript)
5
(No Transcript)
6
(No Transcript)
7
Study Design

• MCL confirmed locally
• Relapsed/refractory to
• 2-7 prior therapies
• Required
• Rituximab
• Anthracycline
• Alkylating agent

Temsirolimus 175 mg q3w then 75 mg qw
Temsirolimus 175 mg q3w then 25 mg qw
RANDOMIZATION
Investigators choice single agent
Temsirolimus treatment to continue until
progression, death or unacceptable toxicity
Protocol specified (n) Gemcitabine i.v. (22),
fludarabine i.v., oral (14), chlorambucil oral
(3), cladribine i.v. (3), etoposide i.v. (3),
cyclophosphamide oral (2)
Approved additions (n) Thalidomide oral (2),
vinblastine i.v. (2)alemtuzumab i.v. (1),
lenalidomide oral (1)
Adapted from Hess et al. ASCO 2008, abstract 8513.
8
Dose Administration and Exposure
Period Temsirolimus 175/75n54 Temsirolimus 175/25n54
Week 1-3 Mean dose intensity, mg/wk Mean relative dose intensity   130 0.74   122 0.70
Week 4 end of treatment Mean dose intensity, mg/wk Mean relative dose intensity   52 0.69   21 0.86
Overall exposure Mean total exposure, mg Mean dose intensity, mg/wk Mean relative dose intensity   1253 84 0.74 757 59 0.80
Adapted from Hess et al. ASCO 2008, abstract 8513.
9
Progression-free Survival (ITT) Excluding
Patients with Blastoid Histology
  Temsirolimus 175/75n54 Temsirolimus 175/25n45 Investigators choicen50
Median PFS, months 4.8 3.5 2.0
95 CI P value vs. IC Hazard ratio 95 CI 4.2-7.4 0.0026 0.47 0.28-0.77 2.0-6.2 0.0464 0.61 0.37-1.00 1.6-2.5
Date of data cutoff 19 July 2007 (independent assessment) Date of data cutoff 19 July 2007 (independent assessment) Date of data cutoff 19 July 2007 (independent assessment) Date of data cutoff 19 July 2007 (independent assessment)
 
Adapted from Hess et al. ASCO 2008, abstract 8513.