6 ADVERSE REACTIONS
The following adverse reactions are described elsewhere in the labeling:
- Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers [see Warnings and Precautions (5.1)]
- Central Nervous System Effects [see Warnings and Precautions (5.2)]
- Hyperlipidemia [see Warnings and Precautions (5.3)]
- Atrioventricular Block [see Warnings and Precautions (5.4)]
- Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.5)]
6.1 Clinical Trials Experience
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 practice.
The data in Warnings and Precautions reflect exposure to LORBRENA in 332 patients with ALK-positive or ROS1-positive, metastatic non-small cell lung cancer (NSCLC) enrolled in a multi-cohort, multinational, non-comparative, dose-finding, and activity-estimating trial (Study B7461001) who received LORBRENA at doses ranging from 10 mg to 200 mg daily in single or divided doses.
The data described below reflect exposure to LORBRENA in 295 patients with ALK-positive or ROS1-positive metastatic NSCLC who received LORBRENA 100 mg orally once daily in Study B7461001. The median duration of exposure to LORBRENA was 12.5 months (1 day to 35 months) and 52% received LORBRENA for ≥12 months. Patient characteristics were a median age of 53 years (19 to 85 years), age ≥65 years (18%), female (58%), White (49%), Asian (37%), and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (96%).
The most common (≥20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. Of the worsening laboratory values occurring in ≥20% of patients, the most common were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.
Serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). Permanent discontinuation of LORBRENA for adverse reactions occurred in 8% of patients.
The most frequent adverse reactions that led to permanent discontinuation were respiratory failure (1.4%), dyspnea (0.7%), myocardial infarction (0.7%), cognitive effects (0.7%) and mood effects (0.7%). Approximately 48% of patients required dose interruption. The most frequent adverse reactions that led to dose interruptions were edema (7%), hypertriglyceridemia (6%), peripheral neuropathy (5%), cognitive effects (4.4%), increased lipase (3.7%), hypercholesterolemia (3.4%), mood effects (3.1%), dyspnea (2.7%), pneumonia (2.7%), and hypertension (2.0%). Approximately 24% of patients required at least 1 dose reduction for adverse reactions. The most frequent adverse reactions that led to dose reductions were edema (6%), peripheral neuropathy (4.7%), cognitive effects (4.1%), and mood effects (3.1%).
Tables 2 and 3 summarize common adverse reactions and laboratory abnormalities, respectively, in patients treated with LORBRENA in Study B7461001.
|Grade 3 or 4|
|Abbreviations: NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; SOC=System organ class.|
|Musculoskeletal and connective tissue|
|Pain in extremity||13||0.3|
|Upper respiratory tract infectionð||12||0|
Additional clinically significant adverse reactions occurring at an incidence between 1% and 10% were hallucinations (7%).
|Grade 3 or 4|
|Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.|
N=number of patients who had at least one on-study assessment for the parameter of interest.
|Increased alkaline phosphatase†||24||1.0|