CARD Trial–Efficacy & Safety Overview

Study Design

A randomized, open-label, multicenter trial in patients (N=255) with mCRPC who previously received docetaxel and had progressed within 12 months on an androgen-signaling-targeted inhibitor—either abiraterone or enzalutamide. These patients were randomized 1:1 to JEVTANA (n=129) or abiraterone or enzalutamide (n=126); patients received abiraterone if they were previously treated with enzalutamide, or enzalutamide if they were previously treated with abiraterone.1,2

mCRPC=metastatic castration-resistant prostate cancer.


46% Relative Reduction in Risk of Radiographic Progression or Death With JEVTANA vs Abiraterone or Enzalutamide1,2

Primary Endpoint: rPFS (Intent-to-treat Population)

All efficacy analyses were performed on the intent-to-treat population, at the cutoff date for 196 rPFS events2

In terms of therapy sequence prior to randomization, rPFS was consistent across the subgroups of patients who received abiraterone/enzalutamide prior to docetaxel (HR=0.61, 95% CI: 0.39-0.96) and those who received abiraterone/enzalutamide after docetaxel (HR=0.48, 95% CI: 0.32-0.70).1

rPFS=radiographic progression-free survival.


Overall Survival (OS) Was Significantly Improved With JEVTANA Compared With Abiraterone or Enzalutamide1,2

Other Efficacy Outcome: OS (Intent-to-treat Population)

At the cutoff date, 153 deaths were noted, with 70 deaths (54.3%) occurring in the JEVTANA 25 mg/m2 group and 83 (65.9%) in the abiraterone or enzalutamide group2




CARD Tumor Response Rate

JEVTANA Delivered a ≥30% Tumor Reduction in 3X More Patients vs Abiraterone or Enzalutamide1,2

Tumor Response (Patients With Measurable Disease at Baseline)1,2

  • Partial response was measured by RECIST criteria, which is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters3

RECIST=Response Evaluation Criteria in Solid Tumors.




CARD Safety

Incidence of ARs With JEVTANA vs Abiraterone or Enzalutamide

ARs* and Hematologic Abnormalities in ≥5% of Patients in the CARD Trial1

  JEVTANA 25 mg/m2 +
prednisone/
prednisolone + G-CSF
(n=126)
abiraterone +
prednisone/
prednisolone or
enzalutamide (n=124)
  JEVTANA 25 mg/m2 +
prednisone/
prednisolone + G-CSF
(n=126)
abiraterone +
prednisone/
prednisolone or
enzalutamide (n=124)
Adverse reactions Grade 1–4   Grade 3–4
Anemia 99% 95%   8% 4.8%
Lymphopenia 72% 55%   27% 17%
Neutropenia 66% 7%   45% 3.2%
Thrombocytopenia 41% 16%   3.2% 1.6%
Fatigue 53% 36%   4% 2.4%
Edema peripheral§ 11% 10%   0.8% 1.6%
Pyrexia 6% 7%   0 0
Pain 6% 6%   0 0.8%
Diarrhea 40% 6%   4.8% 0
Nausea 23% 23%   0 0.8%
Constipation 15% 11%   0 0
Abdominal pain# 14% 6%   1.6% 0.8%
Vomiting 13% 12%   0 1.6%
Stomatitis 8% 1.6%   0 0
Dyspepsia 4.8% 2.4%   0 0
Musculoskeletal pain** 27% 40%   1.6% 6%
Pain in extremity 4.8% 11%   0 2.4%
Bone fracture†† 3.2% 8%   1.6% 2.4%
Infections‡‡ 19% 14%   4% 6%
Peripheral neuropathy§§ 18% 4.8%   1.6% 0
Dysgeusia 11% 4%   0 0
Polyneuropathy 6% 0   1.6% 0
Dizziness 0.8% 4.8%   0 0
Hematuria¶¶ 16% 6%   0.8% 1.6%
Lower urinary tract symptoms## 10% 9%   0 0
Acute kidney injury*** 5% 10%   2.4% 4%
Decreased appetite 14% 15%   0.8% 2.4%
Hypokalemia 3.2% 6%   0 0
Cancer pain 8% 9%   1.6% 2.4%
Cardiac disorders††† 6% 6%   0.8% 3.2%
Pneumonia‡‡‡ 6% 3.2%   1.6% 0.8%
Dyspnea 6% 2.4%   0 0
Alopecia 6% 0   0 0
Fall 4.8% 0   0 0
Hypertension§§§ 4% 8%   2.4% 2.4%
Weight decreased 4% 6%   0 0
Insomnia 3.2% 4.8%   0 0
  JEVTANA 25 mg/m2 +
prednisone/
prednisolone + G-CSF
(n=126)
abiraterone +
prednisone/
prednisolone or
enzalutamide (n=124)
Adverse reactions Grade 1–4
Anemia 99% 95%
Lymphopenia 72% 55%
Neutropenia 66% 7%
Thrombocytopenia 41% 16%
Fatigue 53% 36%
Edema peripheral§ 11% 10%
Pyrexia 6% 7%
Pain 6% 6%
Diarrhea 40% 6%
Nausea 23% 23%
Constipation 15% 11%
Abdominal pain# 14% 6%
Vomiting 13% 12%
Stomatitis 8% 1.6%
Dyspepsia 4.8% 2.4%
Musculoskeletal pain** 27% 40%
Pain in extremity 4.8% 11%
Bone fracture†† 3.2% 8%
Infections‡‡ 19% 14%
Peripheral neuropathy§§ 18% 4.8%
Dysgeusia 11% 4%
Polyneuropathy 6% 0
Dizziness 0.8% 4.8%
Hematuria¶¶ 16% 6%
Lower urinary tract symptoms## 10% 9%
Acute kidney injury*** 5% 10%
Decreased appetite 14% 15%
Hypokalemia 3.2% 6%
Cancer pain 8% 9%
Cardiac disorders††† 6% 6%
Pneumonia‡‡‡ 6% 3.2%
Dyspnea 6% 2.4%
Alopecia 6% 0
Fall 4.8% 0
Hypertension§§§ 4% 8%
Weight decreased 4% 6%
Insomnia 3.2% 4.8%
Adverse reactions Grade 3–4
Anemia 8% 4.8%
Lymphopenia 27% 17%
Neutropenia 45% 3.2%
Thrombocytopenia 3.2% 1.6%
Fatigue 4% 2.4%
Edema peripheral§ 0.8% 1.6%
Pyrexia 0 0
Pain 0 0.8%
Diarrhea 4.8% 0
Nausea 0 0.8%
Constipation 0 0
Abdominal pain# 1.6% 0.8%
Vomiting 0 1.6%
Stomatitis 0 0
Dyspepsia 0 0
Musculoskeletal pain** 1.6% 6%
Pain in extremity 0 2.4%
Bone fracture†† 1.6% 2.4%
Infections‡‡ 4% 6%
Peripheral neuropathy§§ 1.6% 0
Dysgeusia 0 0
Polyneuropathy 1.6% 0
Dizziness 0 0
Hematuria¶¶ 0.8% 1.6%
Lower urinary tract symptoms## 0 0
Acute kidney injury*** 2.4% 4%
Decreased appetite 0.8% 2.4%
Hypokalemia 0 0
Cancer pain 1.6% 2.4%
Cardiac disorders††† 0.8% 3.2%
Pneumonia‡‡‡ 1.6% 0.8%
Dyspnea 0 0
Alopecia 0 0
Fall 0 0
Hypertension§§§ 2.4% 2.4%
Weight decreased 0 0
Insomnia 0 0

ARs=adverse reactions.
*Grade from NCI CTCAE version 4.0.
Based on laboratory values -% calculated using the number of patients with at least one event(n) over the number of patients assessed for each parameter during the on-treatment period.
Includes asthenia, fatigue, lethargy, malaise.
§Includes lymphoedema, edema peripheral, peripheral swelling.
Includes colitis, diarrhea, diarrhea hemorrhagic, gastroenteritis.
#Includes abdominal pain, abdominal pain lower, abdominal pain upper, flank pain, gastrointestinal pain.
**Includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, noncardiac chest pain.
††Includes femoral neck fracture, pathological fracture, rib fracture, spinal compression fracture, sternal fracture, thoracic vertebral fracture.
‡‡Includes bacteremia, bacteriuria, cellulitis, device related sepsis, Enterobacter sepsis, erysipelas, furuncle, influenza, influenza like illness, localized infection, oral fungal infection, perineal cellulitis,
pulmonary sepsis, pyelocaliectasis, pyelonephritis, pyelonephritis acute, respiratory tract infection, respiratory tract infection viral, sepsis, septic shock, subcutaneous abscess, upper respiratory
tract infection, ureteritis, urinary tract infection, urinary tract infection bacterial, urosepsis, viral infection.
§§Includes neuropathy peripheral, paresthesia, peripheral motor neuropathy, peripheral sensorimotor neuropathy, peripheral sensory neuropathy.
¶¶Includes hematuria, cystitis hemorrhagic.
##Includes lower urinary tract symptoms, micturition urgency, nocturia, pollakiuria, urinary incontinence, urinary retention, dysuria.
***Includes acute kidney injury, blood creatinine increased, renal failure, renal impairment.
†††Includes aortic valve incompetence, aortic valve stenosis, atrial fibrillation, atrial flutter, atrioventricular block complete, atrioventricular block second degree, bradycardia, sinus bradycardia,
tachycardia, cardiac failure, acute coronary syndrome, angina pectoris.
‡‡‡Includes lower respiratory tract infection, lung infection, lung infiltration, pneumonia.
§§§Includes hypertension, hypertensive crisis.




No New Safety Signals Were Observed2

ARs of Grade ≥3 Occurred at Similar Rates For Men Receiving JEVTANA as Those Receiving Abiraterone or Enzalutamide (56.3% vs 52.4%)

ARs (Safety Population), No. (%)

  JEVTANA 25 mg/m2
+ prednisone (n=126)
abiraterone or enzalutamide
(n=124)
Any AR 124 (98.4) 117 (94.4)
Grade ≥3 AR 71 (56.3) 65 (52.4)
Serious AR 49 (38.9) 48 (38.7)
AR leading to permanent
treatment discontinuation
25 (19.8) 11 (8.9)
AR leading to death
(fatal outcome)*
7 (5.6) 14 (11.3)

*ARs leading to death were assessed during the period from randomization to 30 days after the last treatment administration.2

Cabazitaxel (JEVTANA) is a National Comprehensive Cancer Network® (NCCN®) designated category 1 2nd-line therapy option in mCRPC after docetaxel and a novel hormonal therapy4

Cabazitaxel (JEVTANA) 25 mg/m2 with concurrent steroid improved rPFS and reduced the risk of death compared with
abiraterone or enzalutamide in mCRPC patients who previously received docetaxel in the CARD trial.