JEVTANA SIDE EFFECTS

  • Generic Name: cabazitaxel injection
  • Brand Name: Jevtana
  • Drug Class: Antineoplastics, Antimicrotubular
Last updated on MDtodate: 10/6/2022

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in another section of the label:

  • Bone Marrow Suppression
  • Increased Toxicities in Elderly Patients
  • Hypersensitivity Reactions
  • Gastrointestinal Adverse Reactions
  • Renal Failure
  • Urinary Disorders Including Cystitis
  • Respiratory Disorders
  • Use in Patients with Hepatic Impairment

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.

TROPIC Trial (JEVTANA + Prednisone Compared To Mitoxantrone)

The safety of JEVTANA in combination with prednisone was evaluated in 371 patients with metastatic castration-resistant prostate cancer treated in the randomized TROPIC trial, compared to mitoxantrone plus prednisone.

Deaths due to causes other than disease progression within 30 days of last study drug dose were reported in 18 (5%) JEVTANA-treated patients and 3 (<1%) mitoxantrone-treated patients. The most common fatal adverse reactions in JEVTANA-treated patients were infections (n=5) and renal failure (n=4). The majority (4 of 5 patients) of fatal infection-related adverse reactions occurred after a single dose of JEVTANA. Other fatal adverse reactions in JEVTANA-treated patients included ventricular fibrillation, cerebral hemorrhage, and dyspnea.

The most common (≥10%) grade 1-4 adverse reactions were anemia, leukopenia, neutropenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, and alopecia.

The most common (≥5%) grade 3-4 adverse reactions in patients who received JEVTANA were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia.

Treatment discontinuations due to adverse drug reactions occurred in 18% of patients who received JEVTANA and 8% of patients who received mitoxantrone. The most common adverse reactions leading to treatment discontinuation in the JEVTANA group were neutropenia and renal failure. Dose reductions were reported in 12% of JEVTANA-treated patients and 4% of mitoxantrone-treated patients. Dose delays were reported in 28% of JEVTANA-treated patients and 15% of mitoxantrone-treated patients.

Table 1: Incidence of Adverse Reactions* and Hematologic Abnormalities in ≥5% of Patients Receiving JEVTANA in Combination with Prednisone or Mitoxantrone in Combination with Prednisone in TROPIC

JEVTANA 25 mg/m2 every 3 weeks with prednisone 10 mg daily
n=371
Mitoxantrone 12 mg/m2 every 3 weeks with prednisone 10 mg daily
n=371
Grade 1-4
n (%)
Grade 3-4
n (%)
Grade 1-4
n (%)
Grade 3-4
n (%)
Any Adverse Reaction
Blood and Lymphatic System Disorders
  Neutropenia 347 (94%) 303 (82%) 325 (87%) 215 (58%)
  Febrile Neutropenia 27 (7%) 27 (7%) 5 (1%) 5 (1%)
  Anemia 361 (98%) 39 (11%) 302 (82%) 18 (5%)
  Leukopenia 355 (96%) 253 (69%) 343 (93%) 157 (42%)
  Thrombocytopenia 176 (48%) 15 (4%) 160 (43%) 6 (2%)
Cardiac Disorders
  Arrhythmia 18 (5%) 4 (1%) 6 (2%) 1 (<1%)
Gastrointestinal Disorders
  Diarrhea 173 (47%) 23 (6%) 39 (11%) 1 (<1%)
  Nausea 127 (34%) 7 (2%) 85 (23%) 1 (<1%)
  Vomiting 83 (22%) 6 (2%) 38 (10%) 0
  Constipation 76 (20%) 4 (1%) 57 (15%) 2 (<1%)
  Abdominal Pain§ 64 (17%) 7 (2%) 23 (6%) 0
  Dyspepsia 36 (10%) 0 9 (2%) 0
General Disorders and Administration Site Conditions
  Fatigue 136 (37%) 18 (5%) 102 (27%) 11 (3%)
  Asthenia 76 (20%) 17 (5%) 46 (12%) 9 (2%)
  Pyrexia 45 (12%) 4 (1%) 23 (6%) 1 (<1%)
  Peripheral Edema 34 (9%) 2 (<1%) 34 (9%) 2 (<1%)
  Mucosal Inflammation 22 (6%) 1 (<1%) 10 (3%) 1 (<1%)
  Pain 20 (5%) 4 (1%) 18 (5%) 7 (2%)
Infections and Infestations
  Urinary Tract Infection# 29 (8%) 6 (2%) 12 (3%) 4 (1%)
Investigations
Weight Decreased 32 (9%) 0 28 (8%) 1 (<1%)
Metabolism and Nutrition Disorders
  Anorexia 59 (16%) 3 (<1%) 39 (11%) 3 (<1%)
  Dehydration 18 (5%) 8 (2%) 10 (3%) 3 (<1%)
Musculoskeletal and Connective Tissue Disorders
  Back Pain 60 (16%) 14 (4%) 45 (12%) 11 (3%)
  Arthralgia 39 (11%) 4 (1%) 31 (8%) 4 (1%)
  Muscle Spasms 27 (7%) 0 10 (3%) 0
Nervous System Disorders
  Peripheral NeuropathyÞ 50 (13%) 3 (<1%) 12 (3%) 3 (<1%)
  Dysgeusia 41 (11%) 0 15 (4%) 0
  Dizziness 30 (8%) 0 21 (6%) 2 (<1%)
  Headache 28 (8%) 0 19 (5%) 0
  Hematuria 62 (17%) 7 (2%) 13 (4%) 1 (<1%)
  Dysuria 25 (7%) 0 5 (1%) 0
Respiratory, Thoracic and Mediastinal Disorders
  Dyspnea 43 (12%) 4 (1%) 16 (4%) 2 (<1%)
  Cough 40 (11%) 0 22 (6%) 0
Skin and Subcutaneous Tissue Disorders
  Alopecia 37 (10%) 0 18 (5%) 0
Vascular Disorders
  Hypotension 20 (5%) 2 (<1 %) 9 (2%) 1 (<1%)
  Median Duration of Treatment 6 cycles 4 cycles
* Graded using NCI CTCAE version 3.
 Based on laboratory values, JEVTANA: n=369, mitoxantrone: n=370.
 Includes atrial fibrillation, atrial flutter, atrial tachycardia, atrioventricular block complete, bradycardia, palpitations, supraventricular tachycardia, tachyarrhythmia, and tachycardia.
§ Includes abdominal discomfort, abdominal pain lower, abdominal pain upper, abdominal tenderness, and GI pain.
 Includes gastroesophageal reflux disease and reflux gastritis.
# Includes urinary tract infection enterococcal and urinary tract infection fungal.
Þ Includes peripheral motor neuropathy and peripheral sensory neuropathy.

 

PROSELICA Trial (Comparison Of Two Doses Of JEVTANA)

In a noninferiority, multicenter, randomized, open-label study (PROSELICA), 1175 patients with metastatic castration-resistant prostate cancer, previously treated with a docetaxel-containing regimen, were treated with either JEVTANA 25 mg/m2 (n=595) or the 20 mg/m2 (n=580) dose.

Deaths within 30 days of last study drug dose were reported in 22 (3.8%) patients in the 20 mg/m2 and 32 (5.4%) patients in the 25 mg/m2 arm. The most common fatal adverse reactions in JEVTANA-treated patients were related to infections, and these occurred more commonly on the 25 mg/m2 arm (n=15) than on the 20 mg/m2 arm (n=8). Other fatal adverse reactions in JEVTANA-treated patients included cerebral hemorrhage, respiratory failure, paralytic ileus, diarrhea, acute pulmonary edema, disseminated intravascular coagulation, renal failure, sudden death, cardiac arrest, ischemic stroke, diverticular perforation, and cardiorenal syndrome.

Grade 1-4 adverse reactions occurring ≥5% more commonly in patients on the 25 mg/m2 versus 20 mg/m2 arms were leukopenia, neutropenia, thrombocytopenia, febrile neutropenia, decreased appetite, nausea, diarrhea, asthenia, and hematuria.

Grade 3-4 adverse reactions occurring ≥5% more commonly in patients on the 25 mg/m2 versus 20 mg/m2 arms were leukopenia, neutropenia, and febrile neutropenia.

Treatment discontinuations due to adverse drug reactions occurred in 17% of patients in the 20 mg/m2 group and 20% of patients in the 25 mg/m2 group. The most common adverse reactions leading to treatment discontinuation were fatigue and hematuria. The patients in the 20 mg/m2 group received a median of 6 cycles (median duration of 18 weeks), while patients in the 25 mg/m2 group received a median of 7 cycles (median duration of 21 weeks). In the 25 mg/m2 group, 128 patients (22%) had a dose reduced from 25 to 20 mg/m2, 19 patients (3%) had a dose reduced from 20 to 15 mg/m2 and 1 patient (0.2%) had a dose reduced from 15 to 12 mg/m2. In the 20 mg/m2 group, 58 patients (10%) had a dose reduced from 20 to 15 mg/m2, and 9 patients (2%) had a dose reduced from 15 to 12 mg/m2.

Table 2: Incidence of Adverse Reactions* in ≥5% of Patients Receiving JEVTANA 20 mg/m2 or 25 mg/m2 in Combination with Prednisone in PROSELICA

JEVTANA 20 mg/m2 every 3 weeks with prednisone 10 mg daily
n=580
JEVTANA 25 mg/m2 every 3 weeks with prednisone 10 mg daily
n=595
Primary System Organ Class Preferred Term Grade 1-4
n (%)
Grade 3-4
n (%)
Grade 1-4
n (%)
Grade 3-4
n (%)
Blood and Lymphatic System Disorders
  Febrile Neutropenia 12 (2%) 12 (2%) 55 (9%) 55 (9%)
  Neutropenia 18 (3%) 14 (2%) 65 (11%) 57 (10%)
Infections and Infestations
  Urinary tract infection 43 (7%) 12 (2%) 66 (11%) 14 (2%)
  Neutropenic infection§ 15 (3%) 13 (2%) 42 (7%) 36 (6%)
Metabolism and Nutrition Disorders
  Decreased appetite 76 (13%) 4 (0.7%) 110 (19%) 7 (1%)
Nervous System Disorders
  Dysgeusia 41 (7%) 0 63 (11%) 0
  Peripheral sensory neuropathy 38 (7%) 0 63 (11%) 4 (0.7%)
  Dizziness 24 (4%) 0 32 (5%) 0
  Headache 29 (5%) 1 (0.2%) 24 (4%) 1 (0.2%)
Respiratory, Thoracic and Mediastinal Disorders
  Dyspnea 30 (5%) 5 (0.9%) 46 (8%) 4 (0.7%)
  Cough 34 (6%) 0 35 (6%) 0
Gastrointestinal Disorders
  Diarrhea 178 (31%) 8 (1%) 237 (40%) 24 (4%)
  Nausea 142 (25%) 4 (0.7%) 191 (32%) 7 (1%)
  Vomiting 84 (15%) 7 (1.2%) 108 (18 %) 8 (1%)
  Constipation 102 (18%) 2 (0.3%) 107 (18%) 4 (0.7%)
  Abdominal pain 34 (6%) 3 (0.5%) 52 (9%) 7 (1%)
  Stomatitis 27 (5%) 0 30 (5%) 2 (0.3%)
Skin and Subcutaneous Tissue Disorders
  Alopecia 15 (3%) 0 36 (6.1%) 0
Musculoskeletal and Connective Tissue Disorders
  Back pain 64 (11%) 5 (0.9%) 83 (14%) 7 (1%)
  Bone pain 46 (8%) 10 (2%) 50 (8%) 13 (2 %)
  Arthralgia 49 (8%) 3 (0.5%) 41 (7%) 5 (0.8%)
  Pain in extremity 30 (5%) 1 (0.2%) 41 (7%) 3 (0.5%)
Renal and Urinary Disorders
  Hematuria 82 (14%) 11 (2%) 124 (21%) 25 (4%)
  Dysuria 31 (5%) 2 (0.3%) 24 (4%) 0
General Disorders and Administration Site Conditions
  Fatigue 143 (25%) 15 (3%) 161 (27%) 22 (4%)
  Asthenia 89 (15%) 11 (2%) 117 (20%) 12 (2%)
  Edema peripheral 39 (7%) 1 (0.2%) 53 (9%) 1 (0.2%)
  Pyrexia 27 (5%) 1 (0.2%) 38 (6 %) 1 (0.2%)
Investigations
  Weight decreased 24 (4%) 1 (0.2%) 44 (7%) 0
Injury, Poisoning and Procedural Complications
  Wrong technique in drug usage process 2 (0.3%) 0 32 (5%) 0
* Grade from NCI CTCAE version 4.03.
 Based on adverse event reporting.
 Includes urinary tract infection staphylococcal, urinary tract infection bacterial, urinary tract infection fungal, and urosepsis.
§ Includes neutropenic sepsis.

 

Table 3: Incidence of Hematologic Laboratory Abnormalities in Patients Receiving JEVTANA 20 mg/m2 or 25 mg/m2 in Combination with Prednisone in Study PROSELICA

Laboratory Abnormality JEVTANA 20 mg/m2 every 3 weeks with prednisone 10 mg daily
n=577
JEVTANA 25 mg/m2 every 3 weeks with prednisone 10 mg daily
n=590
Grade 1-4
n (%)
Grade 3-4
n (%)
Grade 1-4
n (%)
Grade 3-4
n (%)
Neutropenia 384 (67%) 241 (42%) 522 (89%) 432 (73%)
Anemia 576 (99.8%) 57 (10%) 588 (99.7%) 81 (14%)
Leukopenia 461 (80%) 167 (29%) 560 (95%) 351 (60%)
Thrombocytopenia 202 (35%) 15 (3%) 251 (43%) 25 (4%)

 

Hematuria

In study TROPIC, adverse reactions of hematuria, including those requiring medical intervention, were more common in JEVTANA-treated patients. The incidence of grade ≥2 hematuria was 6% in JEVTANA-treated patients and 2% in mitoxantrone-treated patients. Other factors associated with hematuria were well-balanced between arms and do not account for the increased rate of hematuria on the JEVTANA arm.

In study PROSELICA, hematuria of all grades was observed in 18% of patients overall.

Hepatic Laboratory Abnormalities

The incidences of grade 3-4 increased AST, increased ALT, and increased bilirubin were each ≤1%.

Postmarketing Experience

The following adverse reactions have been identified from clinical trials and/or postmarketing surveillance. Because they are reported from a population of unknown size, precise estimates of frequency cannot be made.

Gastrointestinal: Gastritis, intestinal obstruction.

Respiratory: Interstitial pneumonia/pneumonitis, interstitial lung disease and acute respiratory distress syndrome.

Renal and urinary disorders: Radiation recall hemorrhagic cystitis.

 

SRC: NLM .