Toxicity
CheckMate 066rr
Treatment-related adverse events (AEs) of any grade occurred in 74.3% of patients in the nivolumab group and 75.6% of patients in the dacarbazine group. Treatment-related AEs of grade 3/4 occurred in 11.7% of patients in the nivolumab group and 17.6% of patients in the dacarbazine group. The most common AEs in the nivolumab group were fatigue (20%), pruritis (17%) and nausea (16.5%). Treatment-related AEs that led to discontinuation of the study drug occurred in 6.8% of patients in the nivolumab group and 11.7% of patients in the dacarbazine group. No deaths were attributed to study-drug toxicity in either group.r
At the time of 5-year analysis, grade 3/4 treatment-related AEs were reported in 16% of the nivolumab group and 18% of dacarbazine group. Treatment-related AEs that led to treatment discontinuation occurred in 5% and 2% of patients, respectively.r
CheckMate 067rrrr
Treatment related adverse events were reported in 96% of the patients treated with combination therapy, 86% of those treated with nivolumab, and 86% of those treated with ipilimumab. Grade 3 or 4 adverse events occurred in 59%, 21%, and 28%, respectively. Treatment-related adverse events of any grade that led to the discontinuation of therapy occurred more frequently with combination therapy (39%) than with either monotherapy (12% nivolumab, 16% ipilimumab).
The most common select adverse events of grade 3 or 4 were gastrointestinal events, which occurred in 15% of the patients who received combination therapy, in 4% of those who received nivolumab monotherapy, and in 12% of those who received ipilimumab monotherapy (specifically, diarrhoea in 9%, 3%, and 6% of patients respectively).r
Patients have experienced toxicity even after finishing treatment, and deaths considered to be related to study drug >100 days after the last dose.r
At the time of 6.5-year analysis, grade 3/4 treatment-related AEs were reported in 59% of patients treated with combination therapy as compared with 24%, and 28% in the nivolumab and ipilimumab groups, respectively. No new safety signals were detected.r
Treatment related adverse events - Grade 3 or 4 (%) |
CheckMate 066r |
CheckMate 067r |
|
Nivolumab |
Dacarbazine |
Nivolumab |
Nivolumab + ipilimumab |
Ipilimumab |
Total |
16 |
18 |
24 |
59 |
28 |
Fatigue |
0 |
1 |
1 |
4 |
1 |
Pruritus |
<1 |
0 |
<1 |
2 |
<1 |
Nausea |
0 |
0 |
0 |
2 |
1 |
Diarrhoea |
<1 |
<1 |
3 |
10 |
6 |
Rash |
<1 |
0 |
1 |
4 |
2 |
Vomiting |
<1 |
<1 |
<1 |
2 |
<1 |
Hepatitis |
NR |
NR |
3 |
20 |
2 |
Hypothyroidism |
0 |
0 |
0 |
<1 |
0 |
Hypophysitis |
NR |
NR |
<1 |
2 |
2 |
Colitis |
<1 |
0 |
1 |
8 |
8.0 |
Pneumonitis |
<1 |
0 |
<1 |
1 |
<1 |
Renal |
NR |
NR |
1 |
2 |
<1 |
NR= Not reported