1. NCI/CTEP 7435: Eribulin Active, Tolerable in Urothelial Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. Eribulin: Novel Tubulin Inhibitor
Need for new agents in advanced urothelial cancer
Erubulin: a novel tubulin inhibitor that promotes mesenchymal to epithelial transformation
Demonstrated efficacy in phase III trials in breast cancer, soft tissue sarcoma[1,2]
Promising results from single-arm phase I and II trials of eribulin in pts with advanced urothelial cancer, in the first- and second-line settings
Current report on composite results from a single phase II trial in advanced urothelial cancer[3]
1. Cortes J, et al. Lancet. 2011;377: Schöffski P, et al. ASCO Abstract LBA Quinn DI, et al. ASCO Abstract 4504.

3. NCI/CTEP 7435: Eribulin in Advanced Urothelial Carcinoma
A multicenter, single-arm phase II trial
Primary endpoint: ORR ≥ 20%
Secondary endpoints: PFS, 6-mo PFS, OS, toxicity
Stratified by
prior exposure to tubulin inhibitor
Pts with measureable locally advanced or metastatic urothelial cancer; either untreated or ≤ 2 lines previous therapy (at least platinum-based) (N = 150)
Eribulin 1.4 mg/m2 IV
Days 1, 8 of 21-day cycle
IV, intravenous; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
Quinn DI, et al. ASCO Abstract 4504.

4. NCI/CTEP 7435: Baseline Characteristics
Pts (N = 150)
Median age, yrs (range)
67 (37-90)
Male, %
70.7
Race (white/Asian/black/other), %
81/13/2/5
Lower tract as primary site, % 89
Urothelial histology (transitional cell cancer), % 90
Median creatinine clearance, mL/min (range)
56.7 ( )
Renal dysfunction (normal/moderate/severe), %
81/11/8
Visceral metastases, %
69.3
Liver metastases, %
29.3
Quinn DI, et al. ASCO Abstract 4504.

5. NCI/CTEP 7435: Baseline Risk Characteristics
Pts (N = 150)
Karnofsky PS < 90, % 43
MSK Bajorin risk group, % 1 2 29 60 11
Bellmunt risk group, % 3
7.3
36.0
48.0
8.7
MSK, Memorial Sloan Kettering; PS, performance status.
Quinn DI, et al. ASCO Abstract 4504.

6. NCI/CTEP 7435: Eribulin Shows Promising Activity Across All Cohorts
Outcome
All (N = 150)
First Line (n = 52)
Second Line,
Tubulin Naive
(n = 53)
Tubulin Exp
(n = 45)
ORR (CR + PR), %
34.7
46.2
30.1
26.7
SD, %
38.7
38.5
43.4
33.3
Median duration of SD, wks (range)
12 (5-102)
12 (5-43)
12 (6-102)
18 (6-30)
Median OS, mos
9.5
11.3
9.7
8.4
Median PFS, mos
4.1
4.2
3.9
CR, complete response; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SD, stable disease.
Bellmunt, Bajorin risk stratification methods predict PFS, OS in this cohort
Bellmunt classification may be superior as OS predictor; time from last chemotherapy may add information for stratification
Quinn DI, et al. ASCO Abstract 4504.

7. NCI/CTEP 7435: Safety Select AEs of Interest, % Overall (N = 150)
Grade 1
Grade 2
Grade 3
Grade 4
Anemia 38 29 13
Neutropenia 6 15 21 35
Febrile neutropenia 4
Anorexia 10 1
Sensory neuropathy* 33 11
ALT increase 25 5
AST increase 2
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase.
No difference between tubulin-naive, -exposed patients
Older than 70 yrs of age associated with increased risk of grade 3 ≥ AEs, including neutropenia
*18% of pts initiated study with grade 1 neuropathy.
Quinn DI, et al. ASCO Abstract 4504.

8. NCI/CTEP 7435: Conclusions
Eribulin active in both untreated and previously treated advanced urothelial carcinoma
ORR exceeded prespecified 20% boundary for further evaluation
No difference in OS or PFS among cohorts
Tolerable toxicity, with neutropenia and anemia most common ≥ grade 3 AEs
Pts with mild to moderate renal impairment can receive full dosing
Phase III trial comparing eribulin to platinum-containing regimens in advanced urothelial cancer planned
AE, adverse event; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
Quinn DI, et al. ASCO Abstract 4504.

9. Go Online for More CCO Coverage of ASCO 2015!
Short slidesets of all the key data
Additional CME-certified analyses with expert faculty commentary on all the key studies in:
Gastrointestinal cancers
Genitourinary cancer
Hematologic malignancies
Immunotherapy
Lung cancer
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