Lorviqua Adverse Reactions

Summary of safety profile: The data described as follows reflect exposure to LORVIQUA in 476 adult patients with ALK-positive or c-ros oncogene 1 (ROS1)-positive metastatic NSCLC who received LORVIQUA 100 mg orally once daily in single-arm Study B7461001 or randomized, open label, active controlled Phase 3 Study B7461006.
The median duration of treatment was 16.3 months (range: 0 day to 55 months), the median age was 55 years (range: 19 to 90 years), and 25% of patients were older than 65 years. A total of 57% of patients were female, 50% of patients were White, 39% of patients were Asian, and 1% were Black.
The most frequently reported adverse drug reactions were hypercholesterolaemia (81.1%), hypertriglyceridaemia (67.2%), oedema (55.7%), peripheral neuropathy (43.7%), weight increased (30.9%), cognitive effects (27.7%), fatigue (27.3%), arthralgia (23.5%), diarrhoea (22.9%), and mood effects (21.0%).
Serious adverse drug reactions were reported in 7.4% of patients receiving lorlatinib. The most frequent serious adverse drug reactions were cognitive effects and pneumonitis.
Dose reductions due to adverse drug reactions occurred in 20.0% of patients receiving lorlatinib. The most common adverse drug reactions that led to dose reductions were oedema and peripheral neuropathy. Permanent treatment discontinuation associated with adverse drug reactions occurred in 3.2% of patients receiving lorlatinib. The most frequent adverse drug reactions that led to a permanent discontinuation were cognitive effects, peripheral neuropathy, and pneumonitis.
The adverse reactions listed in Table 5 are presented by system organ class and frequency categories, defined using the following convention: very common (≥ 1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to < 1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing medical seriousness. (See Table 5.)

Click on icon to see table/diagram/image

Description of selected adverse drug reactions: Hypercholesterolaemia/Hypertriglyceridaemia: In clinical trials of patients with ALK-positive or c-ros oncogene 1 (ROS1) positive metastatic NSCLC, adverse drug reactions of increase in serum cholesterol or triglycerides were reported in 81.1% and 67.2% of patients, respectively. Mild or moderate adverse drug reactions of hypercholesterolaemia or hypertriglyceridaemia occurred in 62.8% and 47.9% of patients, respectively. No patient was discontinued from treatment with lorlatinib due to hypercholesterolaemia or hypertriglyceridaemia (see Dosage & Administration and Precautions). The median time to onset for both hypercholesterolaemia and hypertriglyceridaemia was 15 days. The median duration of hypercholesterolaemia and hypertriglyceridaemia was 451 and 427 days, respectively.
Central nervous system effects: In clinical trials of patients with ALK-positive or c-ros oncogene 1 (ROS1) positive metastatic NSCLC, CNS adverse drug reactions were primarily cognitive effects (27.7%), mood effects (21.0%), speech effects (8.2%), and psychotic effects (6.9%) and were generally mild, transient, and reversible upon dose delay and/or dose reduction (see Dosage & Administration and Precautions). The most frequent cognitive effect of any grade was memory impairment (11.3%), and the most frequent Grade 3 or 4 reactions were cognitive disorder and confusional state (0.8% and 1.7%, respectively). The most frequent mood effect of any grade was anxiety (6.5%), and the most frequent Grade 3 or 4 reactions were irritability and depression (0.8% and 0.4%, respectively). The most frequent speech effect of any grade was dysarthria (4.0%), and the Grade 3 or 4 reactions were dysarthria, slow speech, and speech disorder (0.2% each). The most frequent psychotic effect of any grade was hallucination (2.9%), and the most frequent Grade 3 or 4 reactions were hallucination auditory and hallucination visual (0.2% each). Median time to onset for cognitive, mood, speech, and psychotic effects was 109, 43, 49 and 23 days, respectively. Median duration of cognitive, mood, speech, and psychotic effects was 223, 143, 147 and 78 days, respectively.