| |
Comparison |
RR |
95% CI low |
ln(RR) |
SE |
p-value |
| Tolerability outcomes |
| Treatment discontinuations due to any cause |
Vemurafenib |
1.15 |
0.88–1.51 |
0.14 |
0.14 |
0.33 |
| Ipilimumab+DTIC |
0.56 |
0.45-0.70 |
-0.58 |
0.11 |
<0.0001 |
| Temozolomide |
0.54 |
0.44-0.68 |
-0.61 |
0.11 |
<0.0001 |
| Treatment discontinuations due to adverse events |
Vemurafenib |
0.75 |
0.12–4.57 |
-0.29 |
0.92 |
0.76 |
| Ipilimumab+DTIC |
0.16 |
0.03-0.87 |
-1.81 |
0.85 |
0.03 |
| Temozolomide |
0.13 |
0.02-0.77 |
–2.01 |
0.89 |
0.02 |
| Safety outcomes |
| General |
| Any adverse events |
Vemurafenib |
0.98 |
0.90–1.07 |
-0.02 |
0.04 |
0.65 |
| Ipilimumab+DTIC |
1.01 |
0.93–1.09 |
0.01 |
0.04 |
0.80 |
| Any serious adverse events |
Vemurafenib |
0.60 |
0.33–1.09 |
-0.51 |
0.30 |
0.10 |
| Any treatment-related adverse events |
Vemurafenib |
0.88 |
0.73–1.05 |
-0.13 |
0.09 |
0.16 |
| Any treatment-related serious adverse events |
Vemurafenib |
0.90 |
0.20–4.03 |
-0.11 |
0.77 |
0.89 |
| Any grade 3/4 adverse events |
Ipilimumab+DTIC |
0.49 |
0.32-0.73 |
-0.72 |
0.21 |
0.0006 |
| Temozolomide |
0.83 |
0.56–1.23 |
-0.19 |
0.20 |
0.35 |
| Adverse events leading to death |
Vemurafenib |
2.65 |
0.11–61.66 |
0.97 |
1.60 |
0.54 |
| Temozolomide |
2.60 |
0.11–60.15 |
0.96 |
1.60 |
0.55 |
| Any dose interruptions/modifications |
Vemurafenib |
0.18 |
0.12-0.28 |
-1.71 |
0.22 |
<0.001 |
| All grades |
| Anemia |
Vemurafenib |
0.41 |
0.13–1.26 |
-0.89 |
0.57 |
0.12 |
| Arthralgia/joint pain |
Vemurafenib |
1.33 |
0.17–10.44 |
0.29 |
1.05 |
0.79 |
| Constipation |
Vemurafenib |
2.22 |
1.00–4.95 |
0.80 |
0.41 |
0.05 |
| Ipilimumab+DTIC |
0.90 |
0.42–1.91 |
-0.11 |
0.38 |
0.78 |
| Cutaneous squamous cell carcinoma |
Vemurafenib |
0.26 |
0.01–7.97 |
-1.35 |
1.75 |
0.44 |
| Decreased appetite |
Vemurafenib |
0.52 |
0.19–1.40 |
-0.65 |
0.50 |
0.20 |
| Ipilimumab+DTIC |
0.99 |
0.39–2.49 |
-0.01 |
0.47 |
0.98 |
| Diarrhea |
Vemurafenib |
0.59 |
0.25–1.39 |
-0.53 |
0.44 |
0.23 |
| Ipilimumab+DTIC |
0.82 |
0.36–1.88 |
-0.19 |
0.42 |
0.65 |
| Fatigue |
Vemurafenib |
0.90 |
0.50–1.60 |
-0.11 |
0.29 |
0.72 |
| Ipilimumab+DTIC |
0.91 |
0.51–1.60 |
-0.10 |
0.29 |
0.74 |
| Headache |
Vemurafenib |
1.79 |
0.69–4.67 |
0.58 |
0.49 |
0.23 |
| Ipilimumab+DTIC |
3.38 |
1.29-8.83 |
1.22 |
0.49 |
0.01 |
| Hyperproliferative skin lesions/hyperkeratosis |
Vemurafenib |
0.20 |
0.01–6.06 |
-1.61 |
1.73 |
0.36 |
| Nausea |
Vemurafenib |
0.73 |
0.49–1.08 |
-0.31 |
0.20 |
0.12 |
| Ipilimumab+DTIC |
0.54 |
0.37-0.79 |
-0.62 |
0.19 |
0.0014 |
| Neutropenia |
Vemurafenib |
3.20 |
0.51–20.12 |
1.16 |
0.94 |
0.22 |
| Palmar-plantar erythrodysesthesia syndrome |
Vemurafenib |
0.65 |
0.04–10.71 |
-0.43 |
1.43 |
0.76 |
| Photosensitivity/phototoxicity |
Vemurafenib |
0.05 |
0.01–0.19 |
-3.00 |
0.73 |
<0.001 |
| Pyrexia/fever |
Vemurafenib |
1.18 |
0.52–2.64 |
0.17 |
0.41 |
0.69 |
| Ipilimumab+DTIC |
0.58 |
0.26–1.29 |
-0.55 |
0.41 |
0.18 |
| Rash |
Vemurafenib |
0.67 |
0.03–13.44 |
-0.40 |
1.53 |
0.79 |
| Ipilimumab+DTIC |
6.21 |
0.37–104.49 |
1.83 |
1.44 |
0.20 |
| Thrombocytopenia |
Vemurafenib |
0.50 |
0.09–2.81 |
-0.69 |
0.88 |
0.43 |
| Vomiting |
Vemurafenib |
1.13 |
0.62–2.06 |
0.12 |
0.31 |
0.70 |
| Ipilimumab+DTIC |
0.63 |
0.35–1.12 |
-0.47 |
0.30 |
0.11 |
| Grades 3 and 4 |
| Anemia |
Temozolomide |
0.10 |
0.01–1.23 |
-2.33 |
1.29 |
0.07 |
| Arthralgia/joint pain |
Vemurafenib |
0.48 |
0.02–13.05 |
-0.73 |
1.68 |
0.67 |
| Cutaneous squamous cell carcinoma |
Vemurafenib |
0.26 |
0.01–7.97 |
-1.35 |
1.75 |
0.44 |
| Decreased appetite |
Ipilimumab+DTIC |
0.08 |
0.00–2.43 |
-2.48 |
1.72 |
0.15 |
| Diarrhea |
Vemurafenib |
0.57 |
0.01–30.83 |
-0.56 |
2.03 |
0.78 |
| Ipilimumab+DTIC |
0.04 |
0.00–3.19 |
-3.10 |
2.18 |
0.15 |
| Fatigue |
Vemurafenib |
1.58 |
0.06–40.06 |
0.46 |
1.65 |
0.78 |
| Ipilimumab+DTIC |
0.70 |
0.03–15.38 |
-0.36 |
1.58 |
0.82 |
| Temozolomide |
1.34 |
0.06–29.08 |
0.30 |
1.57 |
0.85 |
| Hyperproliferative skin lesions/hyperkeratosis |
Vemurafenib |
0.29 |
0.01–18.49 |
-1.24 |
2.11 |
0.56 |
| Leukopenia |
Temozolomide |
0.04 |
0.00-0.78 |
-3.23 |
1.52 |
0.03 |
| Nausea |
Vemurafenib |
1.43 |
0.05–44.73 |
0.36 |
1.76 |
0.84 |
| Ipilimumab+DTIC |
0.71 |
0.02–23.80 |
-0.35 |
1.79 |
0.85 |
| Temozolomide |
0.96 |
0.04–25.40 |
-0.04 |
1.67 |
0.98 |
| Neutropenia |
Vemurafenib |
1.00 |
0.07–13.90 |
0.00 |
1.34 |
1.00 |
| Temozolomide |
0.06 |
0.01-0.51 |
-2.76 |
1.07 |
0.01 |
| Thrombocytopenia |
Temozolomide |
0.06 |
0.01-0.58 |
-2.86 |
1.17 |
0.01 |
| Vomiting |
Vemurafenib |
1.43 |
0.05–41.06 |
0.36 |
1.71 |
0.84 |
| Ipilimumab+DTIC |
0.79 |
0.03–20.19 |
-0.24 |
1.66 |
0.88 |
| Temozolomide |
0.75 |
0.03–17.29 |
-0.28 |
1.60 |
0.86 |
| DTIC: Dacarbazine; SE: Standard Error; RR: Risk Ratio.
aSafety outcomes for all grades and grades 3/4 for dabrafenibvs other interventions, were compared indirectly using a common comparator (DTIC) and based on the safety population. For outcomes in this table: December 2012 data for BREAK-3, October 2011 data for METRIC, and December 2010 data for BRIM-3 were used; text in bold specifies statistically favorable results in favor of dabrafenib; RRs <1 indicate a lower risk/incidence in favor of dabrafenib versus the comparator. |
