1. Intermediate Atypical Carcinoma: Novel Histologic Subtype of mCRPC in Patients Resistant to Androgen Receptor Agonists 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. Androgen Receptor–Targeted Agents for Prostate Cancer
Agents that target androgen receptor have revolutionized treatment of CRPC
Abiraterone: reduces ligand production
Enzalutamide: binds and blocks receptor
However, development of resistance is near-universal and progressive disease frequently leads to death
Limited utility of sequential use of androgen receptor– targeted agents
Small cell/neuroendocrine prostate cancer development is being observed
CRPC, castration-resistant prostate cancer.
Small EJ, et al. ASCO Abstract 5003.

3. West Coast Prostate Cancer Dream Team Project and Trial Design
Consortium of 6 academic medical centers, sought to identify adaptive pathways in metastatic abiraterone- and enzalutamide-resistant prostate cancer
Every-3-Mo Clinical Assessment
Guided Biopsy
Radiology
Optional Biopsy
at Progression
Metastatic CRPC Amenable to biopsy Progressive Disease:
After novel AR targeted rx
“Aggressive phenotype”
On a WCDT trial
Treatment(s)
AR, androgen receptor; BL, baseline; CRPC, castration-resistant prostate cancer; CTCs, circulating tumor cells; rx, prescription; WCDT, West Coast Dream Team.
N = 300
Serum, plasma, and blood for CTCs collected at baseline, 3 mos after therapy begins, and at progression
Small EJ, et al. ASCO Abstract Reprinted with permission.

4. Baseline Characteristics
Characteristics, n (%)
Patients (N = 100)
Gleason score at diagnosis
< 8
≥ 8
53 (42)
72 (58)
Previous treatment for mCRPC
Abiraterone
Enzalutamide
Both
Neither
54 (40)
13 (10)
23 (17)
45 (33)
Metastatic sites
Liver
Other visceral
Bone or lymph node only
24 (20)
18 (15)
77 (64)
No. of prior therapies for advanced disease
≤ 1
≥ 2
Unknown
20 (100)
1 (5)
2 (10)
Median PSA, ng/mL (range)
52 ( )
Median ALP, IU/mL (range)
Median LDH, IU/mL (range)
92 ( )
204 ( )
ALP, alkaline phosphatase; LDH, lactate dehydrogenase; mCRPC, metastatic castration-resistant prostate cancer; PSA, prostate-specific antigen.
Small EJ, et al. ASCO Abstract 5003.

5. Biopsy: Histology Results1% 3% 2%
Histology of 124 Evaluable Biopsies 2% 1%
26%
35%
13%
13%
51%
27%
Mixed histology
Intermediate atypical carcinoma*
Pure
adenocarcinoma
Pure small cell neuroendocrine cancer
Bone (n = 89)
Lymph node (n = 47)
Liver (n = 22)
Lung (n = 2)
Adrenal (n = 3)
Soft tissue (n = 6)
Brain (n = 1)
Bladder (n = 3)
*Novel subtype of pure cell population distinct from adenocarcinoma and small cell neuroendocrine cancer.
Small EJ, et al. ASCO Abstract Reprinted with permission.

6. Intermediate Atypical Carcinoma: Pathology and Survival
New, highly reproducible pathologic subtype by histology, according to consensus of 3 independent histologists
Distributed across bone, lymph node, and liver tissues
No distinct clinical markers identified for this histologic subtype
Serum neuroendocrine marker levels similar in IAC and SCNC and higher than that seen in pts with adenocarcinoma
Chromogranin A, P = .029
Neuron-specific enylase, P = .001
OS by Histology
1.0
Log-rank P = .041
0.8
0.6
Survival Probability
0.4
Adeno (NR) IAC (11.9 mos) SCNC (6.6 mos)
0.2 2 4 6 8 10 12 14 16 18 20 22 24
Adeno, adenocarcinoma; IAC, intermediate atypical carcinoma; NR, not reached; OS, overall survival; SCNC, small-cell neuroendocrine cancer.
Mos
Pts with IAC have poor survival, similar to that seen in pts with SCNC and distinct from that seen in pts with adenocarcinoma (P = .041)
Small EJ, et al. ASCO Abstract Reprinted with permission.

7. Intermediate Atypical Carcinoma: Genomics
In genomic signature analysis, IAC appears as a transitional pattern between SCNC and adenocarcinoma
Associated with intermediate expression of genes used as markers to differentiate these 2 tissue types
In select 50-gene signatures for each histology type, expression of IAC samples fell between SCNC and adenocarcinoma (P < .001)
IAC, intermediate atypical carcinoma; SCNC, small-cell neuroendocrine cancer.
Small EJ, et al. ASCO Abstract 5003.

8. Intermediate Atypical Carcinoma: Conclusion
Intermediate atypical carcinoma is a new histologic subtype of metastatic CRPC
IAC is an aggressive cancer with survival similar to SCNC and distinct from adenocarcinoma
IAC is found in 25% of all biopsies of metastases from CRPC
When combined with SCNC, included in 40% of all samples
IAC and SCNC histologies combined are the largest group of abiraterone and enzalutamide therapy–resistant pts
CRPC, castration-resistant prostate cancer; IAC, intermediate atypical carcinoma; SCNC, small-cell neuroendocrine cancer.
Small EJ, et al. ASCO Abstract 5003.

9. Go Online for More CCO Coverage of ASCO 2015!
Short slidesets of all the key data
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Gastrointestinal cancer
Genitourinary cancer
Hematologic malignancies
Immunotherapy
Lung cancer
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