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 clinical practice.
The safety of INLYTA has been evaluated in 715 patients in monotherapy studies, which included 537 patients with advanced RCC. The data described [see ADVERSE REACTIONS] reflect exposure to INLYTA in 359 patients with advanced RCC who participated in a randomized clinical study versus sorafenib [see Clinical Studies].
The following risks, including appropriate action to be taken, are discussed in greater detail in other sections of the label [see WARNINGS AND PRECAUTIONS]: hypertension, arterial thromboembolic events, venous thromboembolic events, hemorrhage, cardiac failure, gastrointestinal perforation and fistula formation, thyroid dysfunction, wound healing complications, RPLS, proteinuria, elevation of liver enzymes, hepatic impairment and fetal development.
Clinical Trials Experience
The median duration of treatment was 6.4 months (range 0.03 to 22.0) for patients who received INLYTA and 5.0 months (range 0.03 to 20.1) for patients who received sorafenib. Dose modifications or temporary delay of treatment due to an adverse reaction occurred in 199/359 patients (55%) receiving INLYTA and 220/355 patients (62%) receiving sorafenib. Permanent discontinuation due to an adverse reaction occurred in 34/359 patients (9%) receiving INLYTA and 46/355 patients (13%) receiving sorafenib.
The most common ( ≥ 20%) adverse reactions observed following treatment with INLYTA were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation. Table 1 presents adverse reactions reported in ≥ 10% patients who received INLYTA or sorafenib.
Table 1: Adverse Reactions Occurring in ≥ 10% of Patients Who Received INLYTA or Sorafenib
|All Gradesb %||Grade 3/4 %||All Gradesb %||Grade 3/4 %|
|Palmar-plantar erythrodysesthesia syndrome||27||5||51||16|
|Pain in extremity||13||1||14||1|
|aPercentages are treatment-emergent, all-causality events
bNational Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0
Selected adverse reactions (all grades) that were reported in < 10% of patients treated with INLYTA included dizziness (9%), upper abdominal pain (8%), myalgia (7%), dehydration (6%), epistaxis (6%), anemia (4%), hemorrhoids (4%), hematuria (3%), tinnitus (3%), lipase increased (3%), glossodynia (3%), pulmonary embolism (2%), rectal hemorrhage (2%), hemoptysis (2%), deep vein thrombosis (1%), retinal-vein occlusion/thrombosis (1%), polycythemia (1%), and transient ischemic attack (1%).
Table 2 presents the most common laboratory abnormalities reported in ≥ 10% patients who received INLYTA or sorafenib.
Table 2: Laboratory Abnormalities Occurring in ≥ 10% of Patients Who Received INLYTA or Sorafenib
|All Gradesa%||Grade 3/4 %||All Gradesa %||Grade 3/4 %|
|Hemoglobin decreased||320||35||< 1||316||52||4|
|Lymphocytes (absolute) decreased||317||33||3||309||36||4|
|Platelets decreased||312||15||< 1||310||14||0|
|White blood cells decreased||320||11||0||315||16||< 1|
|Creatinine increased||336||55||0||318||41||< 1|
|Bicarbonate decreased||314||44||< 1||291||43||0|
|ALT increased||331||22||< 1||313||22||2|
|AST increased||331||20||< 1||311||25||1|
|Hypoglycemia||336||11||< 1||319||8||< 1|
|aNational Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0
ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase
Selected laboratory abnormalities (all grades) that were reported in < 10% of patients treated with INLYTA included hemoglobin increased (above the upper limit of normal) (9% for INLYTA versus 1% for sorafenib) and hypercalcemia (6% for INLYTA versus 2% for sorafenib).