1. FIRSTANA: Cabazitaxel Not Superior to Docetaxel in Chemotherapy-Naive mCRPC
CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016
*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.
mCRPC, metastatic castration-resistant prostate cancer.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. Cabazitaxel vs Docetaxel in Chemo-Naive mCRPC (FIRSTANA): Background
Cabazitaxel: semisynthetic taxoid compound demonstrating activity against taxane-resistant disease[1-4]
Neutropenia observed as a primary DLT
TROPIC[5] phase III registration trial showed improved OS with cabazitaxel vs mitoxantrone in docetaxel-treated mCRPC
Cabazitaxel subsequently approved for second-line chemo in 2010
FIRSTANA[6] phase III multicenter trial analyzing superiority of cabazitaxel to docetaxel for OS in chemotherapy-naive mCRPC
DLT, dose-limiting toxicity; mCRPC, metastatic castration-resistant prostate cancer.
1. Attard G, et al. Pathol Biol (Paris). 2006;54: Pivot X, et al. Ann Oncol. 2008;19: Mita AC, et al. Clin Cancer Res. 2009;15: Diéras V, et al. Eur J Cancer. 2013;49: de Bono JS, et al. Lancet. 2010;376: Sartor AO, et al. ASCO Abstract 5006.
Slide credit: clinicaloptions.com

3. FIRSTANA: Study Design
Metastatic castration-resistant prostate cancer; ECOG PS 0-2;
no prior chemotherapy, brain mets, or spinal cord compression
(N = 1168)
CBZ 20 mg/m2 q3w +
Prednisone 10 mg/d
(n = 389)
CBZ 25 mg/m2 q3w +
(n = 388)
DOC 75 mg/m2 q3w +
(n = 391)
Pts treated until PD or unacceptable toxicity
CBZ, cabazitaxel; DOC, docetaxel; ECOG, Eastern Cooperative Oncology Group; HRQoL, health-related quality of life; PSA, prostate-specific antigen; PK, pharmacokinetics; PG, pharmacogenomics; PS, performance status.
Primary endpoint: OS
Secondary endpoints: safety, composite PFS,* tumor response, PSA response, pain response, time to skeletal-related events, HRQoL, PK/PG
Exploratory: circulating free DNA level
*PFS determined by progression of PSA, tumor, or pain
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

4. FIRSTANA: Baseline Characteristics
Baseline characteristics well balanced across treatment arms
Characteristic
CBZ 20 + PRED
(n = 389)
CBZ 25 + PRED
(n = 388)
DOC + PRED
(n = 391)
Median age, yrs (range)
68.0 (44-90)
68.5 (42-85)
69.0 (41-87)
White race, %
93.8
92.8
ECOG PS 0-1, %
95.6
95.9
95.7
Median time from diagnosis to first dose, mos
46.9
36.7
45.7
Median PSA, ng/mL
76.00
80.04
73.92
Metastases, %
Bone
Lymph nodes
Lung
Liver
88.7
53.2
14.9
8.2
88.9
53.6
12.9
10.1
91.0
54.0
12.0
9.0
CBZ, cabazitaxel; DOC, docetaxel; ECOG, Eastern Cooperative Oncology Group; PRED, prednisone; PS, performance status; PSA, prostate-specific antigen.
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

5. FIRSTANA: Treatment History/Exposure
Characteristic
DOC + PRED
(n = 391)
CBZ 20 + PRED
(n = 389)
CBZ 25 + PRED
(n = 388)
Prior hormonal therapy, % 1 2
≥ 3
97.7
38.4
26.9
32.5
97.4
37.8
22.4
37.3
98.7
36.9
27.8
34.0
Radical prostatectomy, %
21.7
25.4
20.1
Radiation, %
49.9
57.3
50.0
Next-gen AR-targeted drugs, %
Enzalutamide
Abiraterone acetate
97.2
0.8
2.0
95.9
1.0
0.5
Median no. cycles/pt 9
Mean relative dose intensity
0.94
0.92
≥ 1 dose delay and/or reduction, %
50.4
59.8
≥ 1 cycle at reduced dose, %
25.6
13.6
35.8
CBZ, cabazitaxel; DOC, docetaxel; PRED; prednisone; AR, androgen receptor.
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

6. FIRSTANA: Response PSA Response Rate* Tumor Response Rate† P = .0524
100 60
P = .9993
P = .0370 50 80 40 60
Pts (%) 30 40 20
68.4
242/354
60.7
210/346
68.7
235/342
30.9
54/175
32.4
61/188
41.6
72/173 20 10
n/N
BL, baseline; CBZ, cabazitaxel; DOC, docetaxel; PRED, prednisone; PSA, prostate-specific antigen; RECIST, Response Evaluation Criteria in Solid Tumors.
DOC + PRED
CBZ 20 + PRED
CBZ 25 + PRED
DOC + PRED
CBZ 20 + PRED
CBZ 25 + PRED
*Assessed in pts with BL PSA ≥ 10 ng/mL and ≥ 1 post-BL measurement.
†Assessed in pts with BL measurable disease meeting RECIST criteria for analysis.
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract Reproduced with permission.

7. FIRSTANA: Progression-Free Survival
100
DOC + PRED CBZ 20 + PRED
CBZ 25 + PRED
Median PFS, Mos (95% CI) DOC + PRED 5.3 ( ) CBZ 20 + PRED 4.4 ( )
CBZ 25 + PRED 5.1 ( ) CBZ 20 vs DOC HR (95% CI: ; P = )
CBZ 25 vs DOC HR: (95% CI: ; P = ) 80 60
PFS (%) 40 20
CBZ, cabazitaxel; DOC, docetaxel; PRED, prednisone. 3 6 9 12 15 18 21 24 27 30 33 36
Mos
Small observed difference in pain progression component of PFS for CBZ 25 vs DOC (P = .0354) but likely not clinically significant
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

8. FIRSTANA: Overall Survival
Median OS, Mos (95% CI) DOC + PRED ( ) CBZ 20 + PRED ( )
CBZ 25 + PRED ( ) CBZ 20 vs DOC HR: (95% CI: ;
P = .9967)
CBZ 25 vs DOC HR: 0.97 (95% CI: ;
P = .7574)
100
DOC + PRED CBZ 20 + PRED
CBZ 25 + PRED 80 60
OS (%) 40 20
CBZ, cabazitaxel; DOC, docetaxel; PRED, prednisone. 36 6 12 18 24 30 42 48 54
Mos
OS and PFS statistically comparable for each CBZ arm vs DOC
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

9. FIRSTANA: Treatment-Emergent AEs
DOC + PRED
(n = 387)
CBZ 20 + PRED
(n = 369)
CBZ 25 + PRED
(n = 391)
Any grade
97.2
95.9
96.2
Grade 3/4
46.0
41.2
60.1
Serious
32.6
34.4
47.6
Leading to discontinuation
33.9
25.2
31.7
Select any grade occurring in ≥ 5% of pts
Febrile neutropenia
Neutropenic infection
Diarrhea
Stomatitis
Hematuria
Peripheral neuropathy
Peripheral edema
Alopecia
Nail disorder
8.3
4.9
37.0
13.7
3.6
25.1
20.4
39.0
9.0
2.4
1.6
32.5
20.3
11.7
9.8
8.9
0.3
12.0
6.1
49.9
6.6
12.3
7.7
13.0
0.8
AE, adverse event; CBZ, cabazitaxel; DOC, docetaxel; PRED, prednisone
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

10. FIRSTANA: Gr 3/4 Hematologic Toxicity and Mortality
Characteristic, %
DOC + PRED
(n = 387)
CBZ 20 + PRED
(n = 369)
CBZ 25 + PRED
(n = 391)
Grade 3/4 lab abnormalities
Neutropenia
Anemia
Thrombocytopenia
78.9
5.5
1.6
37.8
6.5
70.6
8.7
3.1
Death within 30 days of last dose
2.7
4.1
Any death before/after tx
Disease progression
Adverse event
66.9
58.1
2.1
68.8
61.5
1.1
63.7
51.9
CBZ, cabazitaxel; DOC, docetaxel; PRED, prednisone; tx, treatment.
Possible myelosuppression differences between CBZ doses
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

11. FIRSTANA: Conclusions
Study did not show superiority in OS of either dose of CBZ vs DOC
PFS, OS statistically comparable across treatments
Response rates similar with CBZ25 dose demonstrating superior tumor response via RECIST criteria
Different toxicity profiles noted for CBZ vs DOC
However, no new safety concerns
Study investigators suggest that 2 different taxanes may offer similar activity but with different safety profiles in mCRPC
CBZ, cabazitaxel; DOC, docetaxel; mCRPC, metastatic castration-resistant prostate cancer; RECIST, Response Evaluation Criteria in Solid Tumors.
Slide credit: clinicaloptions.com
Sartor AO, et al. ASCO Abstract 5006.

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