REVEL Safety Profile
31% of patients (195 out of 627) in the REVEL trial received CYRAMZA for at least 6 months1
- Median duration of exposure was 3.5 months (median of 4.5 doses)
Discontinuation of CYRAMZA/placebo due to ≥1 TEAE was 1.4% (n=9) in the CYRAMZA plus docetaxel arm vs 1% (n=6) in the placebo plus docetaxel arm. Discontinuation of docetaxel due to ≥1 TEAE was 7.8% (n=49) vs 4.2% (n=26)2
- Treatment discontinuation due to adverse reactions occurred more frequently in CYRAMZA plus docetaxel-treated patients (9%) than in placebo plus docetaxel-treated patients (5%)
- The median relative dose intensity was 98.0% for CYRAMZA and 98.7% for placebo. The median relative dose intensity of docetaxel was 93.5% for the CYRAMZA plus docetaxel arm and 96.5% for placebo plus docetaxel arm3
- 51% (n=320/628) of patients received ≥1 subsequent therapy post-discontinuation with CYRAMZA plus docetaxel vs 55% (n=343/625) of patients for placebo plus docetaxel4
- The most common serious adverse reactions in patients who received CYRAMZA with docetaxel were febrile neutropenia (14%), pneumonia (6%), and neutropenia (5%). The use of granulocyte colony-stimulating factors was 42% in CYRAMZA with docetaxel-treated patients versus 37% in patients who received placebo with docetaxel.
- The most common adverse reactions leading to treatment discontinuation of CYRAMZA were infusion-related reaction (0.5%) and epistaxis (0.3%). For patients with non-squamous histology, the overall incidence of pulmonary hemorrhage was 7% and the incidence of Grade ≥3 pulmonary hemorrhage was 1% for CYRAMZA with docetaxel compared to 6% overall incidence and 1% for Grade ≥3 pulmonary hemorrhage for placebo with docetaxel. For patients with squamous histology, the overall incidence of pulmonary hemorrhage was 10% and the incidence of Grade ≥3 pulmonary hemorrhage was 2% for CYRAMZA with docetaxel compared to 12% overall incidence and 2% for Grade ≥3 pulmonary hemorrhage for placebo with docetaxel. Treatment discontinuation due to adverse reactions occurred more frequently in CYRAMZA with docetaxel-treated patients (9%) than in placebo with docetaxel-treated patients (5%).
- The most common adverse reactions (all grades) observed in CYRAMZA with docetaxel-treated patients at a rate of ≥30% and ≥2% higher than placebo with docetaxel were neutropenia, fatigue/asthenia, and stomatitis/mucosal inflammation.
- Clinically relevant adverse drug reactions reported in ≥1% and <5% of CYRAMZA with docetaxel-treated patients in REVEL were hyponatremia (4.8%) and proteinuria (3.3%).
The rate of adverse events* observed in the rapidly progressing disease† subpopulations was consistent with that observed in the overall safety population‡5,6
For patients in the overall safety population, discontinuation rates due to TEAEs were 9% (n=58) in the CYRAMZA plus docetaxel arm vs 5% (n=32) in the placebo plus docetaxel arm.6
For patients with rapidly progressing disease,† discontinuation rates due to TEAEs were 5% (n=5) in the CYRAMZA + docetaxel arm vs 3% (n=3) in the placebo + docetaxel arm.5
SAFETY OVERVIEW FOR THE OVERALL SAFETY POPULATION6
SAFETY OVERVIEW FOR PATIENTS IN THE RAPID PROGRESSION† SUBGROUPS5
REVEL Exploratory Analyses5,6:
The REVEL trial was not adequately powered or error-controlled for subgroup analyses. No formal hypotheses regarding safety outcomes were tested in the REVEL trial. The analyses described here were post hoc and exploratory.
Incidence of pulmonary hemorrhage by histology (REVEL trial)1
Pulmonary Hemorrhage by Histology
Additional adverse events to consider with CYRAMZA as an antiangiogenic therapy7
Clinically Relevant Adverse Events Associated with Antiangiogenic Therapy
Ramucirumab inhibited angiogenesis in an in vivo animal model