AusPAR: Cabazitaxel - Therapeutic Goods Administration

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AusPAR Jevtana Cabazitaxel Sanofi-Aventis Australia Pty Ltd PM-2010-02565-3-4 Final 9 February 2012 Therapeutic Goods Administration neutropenia, diarrhoea and pneumonia. In the mitoxantrone arm, the most common SAEs were disease progression and pulmonary embolism (Table 14). Table 14: Number (%) of patients experiencing a serious adverse event at a percentage >=1% in any treatment group - by preferred term (worst grade by patient) - safety population Other studies The incidence of patient deaths in the Phase I/Phase II studies was similar to that in the pivotal study. Most of the deaths were due to disease progression. There were 4 deaths due to TEAEs within 30 days of the last dose and 1 from an unknown cause. In the combination study TCD 6945, 4 deaths occurred during the study due to disease progression. Serious adverse events were reported in 28 (31.5%), and 16 (37.2%) patients in the ≤ 25 mg/m 2 and ≥ 25 mg/m 2 groups respectively and in 25 (45.5%) patients in the weekly group. Febrile neutropenia and diarrhoea were the most common causes of death. In the combination study, SAEs were reported in 17 patients. There was no pattern to the SAEs. Discontinuation due to adverse events Pivotal study In all 68 patients (18.3%) in the cabazitaxel arm and 31 patients (8.4%) in the mitoxantrone arm withdrew from the study due to AEs. The most common causes of discontinuation in the cabazitaxel arm were neutropenia, febrile neutropenia, haematuria, diarrhoea, fatigue, renal failure and sepsis. One patient discontinued from the study because of Grade 3 peripheral sensory neuropathy. In the mitoxantrone arm, the most common causes were asthenia, back pain, pulmonary embolism, cardiotoxicity including a Page 46 of 75
AusPAR Jevtana Cabazitaxel Sanofi-Aventis Australia Pty Ltd PM-2010-02565-3-4 Final 9 February 2012 Therapeutic Goods Administration decreased ejection fraction. There was one discontinuation due to Grade 3 peripheral sensory neuropathy. Other studies There were 16 discontinuations in the Phase I/Phase II studies. The reasons for discontinuation were similar to those in the pivotal study. In the combination study, there were 9 discontinuations due to TEAEs. These included haematological and renal causes and neutropenia. Laboratory tests Clinical chemistry Pivotal and other studies The proportion of patients with clinical chemistry abnormalities Grade ≥3 was similar in the two arms of the study. The incidence of clinical chemistry abnormalities in patients in the Phase I/Phase II studies was higher than in the pivotal study but they were mostly Grade 1/2. In the combination study, the incidence of clinical chemistry abnormalities was high, but the abnormalities were mainly Grades 1/2. Liver function Pivotal and other studies The incidence of abnormal LFTs was generally similar between the two arms of the pivotal study. The incidence of abnormal LFTs was higher in patients in the Phase I/ Phase II studies but most of the increase was in Grades ≤2 abnormalities. Renal and urinary disorders Pivotal and other studies Renal and urinary disorders were more frequent in the cabazitaxel arm than in the mitoxantrone arm (30.7% vs 11.3%). Renal failure and impairment was reported in 4% of patients in the cabazitaxel arm and 0.8% of those in the mitoxantrone arm and severe renal failure and impairment was reported in 3.2% of patients in the cabazitaxel arm and 0.3% in the mitoxantrone arm. Of the 15 patients in the cabazitaxel arm with acute renal failure, 8 patients recovered and 7 failed to recover. Serum creatinine increases in the Phase I/ Phase II studies in patients with normal values at baseline were similar to that in the pivotal study. Haematology Pivotal and other studies Myelosuppression, resulting in neutropenia and anaemia, was more frequently reported in the cabazitaxel arm than in the mitoxantrone arm. Grade ≥3 neutropenia was reported in 81.7% of patients in the cabazitaxel arm and 58% of those in the mitoxantrone arm. The first occurrence of neutropenia in the cabazitaxel arm was within the first 2 weeks in 70 to 80 % of patients (Figure 9). Page 47 of 75
Page 1 and 2: Australian Public Assessment Report
Page 3 and 4: Contents AusPAR Jevtana Cabazitaxel
Page 5 and 6: AusPAR Jevtana Cabazitaxel Sanofi-A
Page 7 and 8: Acetone Solvate AusPAR Jevtana Caba
Page 17 and 18: Toxicological effects typical of th
Page 19 and 20: Reproductive toxicity AusPAR Jevtan
Page 21 and 22: Table 3: Details of impurities test
Page 29 and 30: Figure 1: Flow chart AusPAR Jevtana
Page 33 and 34: Figure 2: Overall survival (OS) - I
Page 45: AusPAR Jevtana Cabazitaxel Sanofi-A
Page 55 and 56: Safety AusPAR Jevtana Cabazitaxel S
Page 59 and 60: NAME OF THE MEDICINE Non-proprietar
Page 61 and 62: CLINICAL TRIALS The efficacy and sa
Page 63 and 64: Table 2 Efficacy of Jevtana in the
Page 65 and 66: Risk of cardiac arrhythmias Cardiac
Page 67 and 68: co-administration with CYP3A induce
Page 69 and 70: System Organ Class Adverse Reaction
Page 71 and 72: none of which were Grade ≥3. The
Page 73 and 74: Table 4 Recommended Dosage Modifica
Page 75: Therapeutic Goods Administration PO

AusPAR: Cabazitaxel - Therapeutic Goods Administration

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