Adverse Reaction Profile for CYRAMZA in Combination with Docetaxel1
- 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.