erapy are administered during the treatment period, Xofigo should be discontinued.
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in another section of the label:
•
Bone Marrow Suppression [see Warnings and Precautions (5.1)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the randomized clinical trial in patients with metastatic castration-resistant prostate cancer with bone metastases, 600 patients received intravenous injections of 50 kBq/kg (1.35 microcurie/kg) of Xofigo and best standard of care and 301 patients received placebo and best standard of care once every 4 weeks for up to 6 injections. Prior to randomization, 58% and 57% of patients had received docetaxel in the Xofigo and placebo arms, respectively. The median duration of treatment was 20 weeks (6 cycles) for Xofigo and 18 weeks (5 cycles) for placebo.
The most common adverse reactions (≥ 10%) in patients receiving Xofigo were nausea, diarrhea, vomiting, and peripheral edema (Table 3). Grade 3 and 4 adverse events were reported among 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in Xofigo-treated patients (≥ 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia (Table 4).
Treatment discontinuations due to adverse events occurred in 17% of patients who received Xofigo and 21% of patients who received placebo. The most common hematologic laboratory abnormalities leading to discontinuation for Xofigo were anemia (2%) and thrombocytopenia (2%).
Table 3 shows adverse reactions occurring in ≥ 2% of patients and for which the incidence for Xofigo exceeds the incidence for placebo.
Table 3: Adverse Reactions in the Randomized Trial System/Organ Class
Preferred Term
Xofigo (n=600)
Placebo (n=301)
Grades 1-4
%
Grades 3-4
%
Grades 1-4
%
Grades 3-4
%
Blood and lymphatic system disorders
Pancytopenia
2
1
0
0
Gastrointestinal disorders
Nausea
36
2
35
2
Diarrhea
25
2
15
2
Vomiting
19
2
14
2
General disorders and administration site conditions
Peripheral edema
13
2
10
1
Renal and urinary disorders
Renal failure and impairment
3
1
1
1
Laboratory Abnormalities
Table 4 shows hematologic laboratory abnormalities occurring in > 10% of patients and for which the incidence for Xofigo exceeds the incidence for placebo.
Table 4: Hematologic Laboratory Abnormalities
Hematologic Laboratory Abnormalities
Xofigo (n=600)
Placebo (n=301)
Grades 1-4
%
Grades 3-4
%
Grades 1-4
%
Grades 3-4
%
Anemia
93
6
88
6
Lymphocytopenia
72
20
53
7
Leukopenia
35
3
10
<1
Thrombocytopenia
31
3 |
