1. ASPEN: Prolonged PFS With Sunitinib vs Everolimus in Nonclear-Cell RCC 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.
PFS, progression-free survival; RCC, renal cell carcinoma.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. ASPEN: Background
Limited evidence for treatment of heterogeneous population of NCRCC
Randomized trials needed to develop standard of care
Previous evidence that temsirolimus prolonged OS vs interferon in NCRCC[1]
ASPEN: randomized phase II trial comparing everolimus vs sunitinib in metastatic NCRCC[2]
Largest randomized trial in NCRCC to date
Designed to inform practice and explore predictive biomarkers
NCRCC, nonclear-cell renal cell carcinoma; OS, overall survival.
1. Hudes G, et al. N Engl J Med. 2007;356: Armstrong AJ, et al. ASCO Abstract 4507.

3. ASPEN: Everolimus vs Sunitinib in NCRCC
Stratified by histology (papillary vs chromophobe vs unclassified), MSKCC risk group
Everolimus 10 mg QD
daily in 6-wk cycles
(n = 57)
Untreated pts with metastatic NCRCC, KPS ≥ 60
(N = 108)
Sunitinib 50 mg QD
Days 1-28 in 6-wk cycles
(n = 51)
CBR, clinical benefit rate; KPS, Karnofsky performance status; MSKCC, Memorial Sloan–Kettering Cancer Center; NCRCC, nonclear-cell renal cell carcinoma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; QD, once daily; QoL, quality of life.
Primary endpoint: radiographic PFS
Secondary endpoints: OS; PFS at 6, 12, 24 mos; ORR; CBR; time to metastasis; QoL
Armstrong AJ, et al. ASCO Abstract 4507.

4. ASPEN: Pt Baseline Characteristics
Sunitinib (n = 51)
Everolimus (n = 57)
Male, % 73 77
Median age, yrs (range)
59 (24-100)
64 (29-90)
Papillary histology (type 1), %
65 (8)
65 (4)
Chromophobe, % 20 11
Unclassified histology, % 16 23
Translocation carcinoma, % 12 4
Sarcomatoid differentiation, % 27
Prior nephrectomy, % 80 79
MSKCC risk group, %
1-2
≥ 3 29 63 8 25 56 19
MSKCC, Memorial Sloan Kettering Cancer Center.
Armstrong AJ, et al. ASCO Abstract 4507.

5. ASPEN: Progression-Free Survival
1.0
0.8
0.6
0.4
0.2
Sunitinib, median PFS 8.3 mos
Everolimus, median PFS 5.6 mos
Stratified log-rank HR 1.41, P = .16 < 0.20 boundary P value
Probability of PFS
NR, not reached; OS, overall survival; PFS, progression-free survival. 6 12 18 24 30 36 51 57 26 21 17 8 10 4 3 2 1
Sunitinib
Everolimus
Pts at Risk, n
Mos
Median OS: sunitinib vs everolimus: 32 (95% CI: 15-NR) vs 13 mos (95% CI: ) (HR: 1.12; P = .60)
Armstrong AJ, et al. ASCO Abstract Reprinted with permission.

6. ASPEN: PFS by Prespecified Pt Subgroups
Category
Median PFS (S vs. E, mos)
HR (80% CI)
Overall
8.3 vs. 5.6
1.41 ( )
Good risk
14 vs. 5.7
3.07 ( )
Int. Risk
6.5 vs. 4.9
1.38 ( )
Poor Risk
4.0 vs. 6.1
0.21 ( )
Papillary
8.1 vs. 5.5
1.52 ( )
Chromophobe
5.5 vs. 11.4
0.71 ( )
Unclassified
11.5 vs. 5.6
2.55 ( )
E, everolimus; PFS, progression-free survival; S, sunitinib.
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
HR and 80% CI
Favors everolimus
Favors sunitinib
Armstrong AJ, et al. ASCO Abstract Reprinted with permission.

7. ASPEN: Tumor Response by RECIST 1.1
Sunitinib (n = 51)
Everolimus (n = 57)
Best overall response, %
CR/PR SD PD
Not evaluated 18 59 19 4 9 53 23 15
Clinical benefit response (CR + PR + SD ≥ 24 wks), % 22 11
Best tumor change, median %
+10.7
+2.1
Median duration of response, mos
5.5
3.3
CR, complete response; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.
Sunitinib associated with larger clinical response but more tumor growth
Armstrong AJ, et al. ASCO Abstract 4507.

8. ASPEN: Select Adverse Events
Sunitinib (n = 51)
Everolimus (n = 57)
All
Grade ≥ 3
Nausea 71
5.9 46
1.8
Diarrhea 67
9.8 30
Hypertension 45
23.5 11
Hand–foot syndrome 41
7.8 14
Stomatitis 28 47
8.8
Peripheral edema 16 2 26
Pneumonitis 18
Hypertriglyceridemia 5
Hyperglycemia 8 12
Everolimus: more discontinuations due to toxicity (23% vs 14%)
Armstrong AJ, et al. ASCO Abstract 4507.

9. ASPEN: Conclusions
Sunitinib significantly prolonged PFS compared to everolimus in previously untreated metastatic NCRCC
Pts with MSKCC good/intermediate risk status, papillary histology, and unclassified subtype had improved PFS with sunitinib
Pts with MSKCC poor risk status and chromophobe histology had improved PFS with everolimus
Short survival times and low response rates to both agents highlight continuing medical need for new treatment approaches in this pt population
MSKCC, Memorial Sloan Kettering Cancer Center; NCRCC, nonclear-cell renal cell carcinoma; PFS, progression-free survival.
Armstrong AJ, et al. ASCO Abstract 4507.

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