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.

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;54:72-84. 2. Pivot X, et al. Ann Oncol. 2008;19:1547-1552. 3. Mita AC, et al. Clin Cancer Res. 2009;15:723-730. 4. Diéras V, et al. Eur J Cancer. 2013;49:25-34. 5. de Bono JS, et al. Lancet. 2010;376:1147-1154.6.Sartor AO, et al. ASCO 2016. Abstract 5006. Slide credit: clinicaloptions.com

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 2016. Abstract 5006.

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 2016. Abstract 5006.

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 2016. Abstract 5006.

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 2016. Abstract 5006. Reproduced with permission.

FIRSTANA: Progression-Free Survival 100 DOC + PRED CBZ 20 + PRED CBZ 25 + PRED Median PFS, Mos (95% CI) DOC + PRED 5.3 (4.86-5.78) CBZ 20 + PRED 4.4 (3.91-5.09) CBZ 25 + PRED 5.1 (4.60-5.72) CBZ 20 vs DOC HR 1.062 (95% CI: 0.913-1.236; P = .4218 ) CBZ 25 vs DOC HR: 0.989 (95% CI: 0.849-1.152; P = .80350) 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 2016. Abstract 5006.

FIRSTANA: Overall Survival Median OS, Mos (95% CI) DOC + PRED 24.3 (22.18-27.60) CBZ 20 + PRED 24.5 (21.75-27.20) CBZ 25 + PRED 25.2 (22.90-26.97) CBZ 20 vs DOC HR: 1.009 (95% CI: 0.85-1.197; P = .9967) CBZ 25 vs DOC HR: 0.97 (95% CI: 0.819-1.160; 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 2016. Abstract 5006.

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 2016. Abstract 5006.

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 2016. Abstract 5006.

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 2016. Abstract 5006.

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