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The safety of ROZLYTREK in adult patients has been evaluated in a total of 475 patients with NTRK-fusion positive, ROS1-positive or ALK-positive solid tumors, in studies ALKA, STARTRK-1, and STARTRK-2.
The safety of ROZLYTREK has been evaluated in 29 pediatric patients with solid tumors (27 patients enrolled in STARTRK-NG, and 2 patients enrolled in STARTRK-2). Of these, 1 patient was less than 1 year old, 21 patients were 2 to 11 years old, 7 patients were 12 to 17 years old.
Tabulated summary of adverse drug reactions from clinical trials: Table 13 summarizes the adverse drug reactions (ADRs) occurring in adult and pediatric patients treated with ROZLYTREK. Adverse drug reactions from clinical trials are listed by MedDRA system organ class. The following categories of frequency have been used: very common ≥1/10, common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to < 1/1000), very rare (<1/10,000). (See Table 13.)
Click on icon to see table/diagram/imageDescription of selected adverse drug reactions: Cognitive disorders: A variety of cognitive symptoms were reported across clinical trials (see General under Precautions). These included events reported as cognitive disorders (6.3%), confusional state (7.3%), disturbance in attention (3.8%), memory impairment (4.2%), amnesia (2.8%), mental status changes (1.2%), hallucination (1.0%), delirium (0.8%), hallucination visual (0.4%) and mental disorder (0.2%). Grade 3 events were reported in 4.4% of patients. In the pediatric population, 3.4% (1/29) pediatric patients experienced disturbance in attention of Grade 1 severity. Patients who had brain metastases at baseline had a higher frequency of these events (29.7%) compared to those without brain metastases (23.1%).
Fractures: Fractures were experienced by 5.3% (N=475) of adult patients and 20.7% (N=29) of pediatric patients. In general, there was inadequate assessment for tumour involvement at the site of fracture; however, radiologic abnormalities possibly indicative of tumour involvement were reported in some patients. In both adult and pediatric patients, most fractures were hip or other lower extremity fractures (e.g., femoral or tibial shaft). In 2 pediatric patients, bilateral femoral neck fractures occurred. No patients discontinued Rozlytrek due to fractures.
In adult patients, some fractures occurred in the setting of a fall or other trauma to the affected area. The median time to fracture was 3.42 months (range: 0.26 months to 18.5 months) in adults. Rozlytrek was interrupted due to fractures in 36.0% of adult patients that experienced fractures.
In pediatric patients, all fractures occurred in patients with minimal or no trauma. The median time to fracture was 3.38 months (range: 1.77 months to 7.39 months) in pediatric patients. Rozlytrek was interrupted due to fractures in 33.3% of pediatric patients that experienced fractures.
Ataxia: Ataxia (including events of ataxia, balance disorder, and gait disturbances) was reported in 15.7% of patients. The median time to onset for ataxia was 0.36 months (range: 0.03 months to 28.19 months) and the median duration was 0.66 months (range: 0.03 months to 11.99 months). The majority of patients (67.1%) recovered from ataxia. Ataxia related adverse events were observed more frequently in elderly patients (23.8%) compared to patients below 65 years of age (12.8%).
Syncope: Syncope events were reported in 4.6% of patients. In some patients, syncope was reported with concurrent hypotension, dehydration, or QTc prolongation and in other patients no other concurrent related conditions were reported.
QTc interval prolongation: Among the 504 patients who received entrectinib across clinical trials, 17 (4.0%) patients with at least one post-baseline ECG assessment experienced QTcF interval prolongation of > 60 ms after starting entrectinib, and 12 (2.8%) patients had a QTcF interval of ≥500 ms.
Peripheral sensory neuropathy: Peripheral sensory neuropathy was reported in 15.7% of patients. The median time to onset was 0.49 months (range 0.03 months to 20.93 months) and the median duration was 0.76 months (range: 0.07 months to 6.01 months). The majority of patients (55.7%) recovered from peripheral neuropathy.
Eye Disorders: Eye disorders reported across clinical trials included events of vision blurred (8.5%), diplopia (2.6%), and visual impairment (1.6%). The median time to onset for eye disorders was 1.87 months (range: 0.03 months to 21.59 months). The median duration of eye disorders was 1.02 months (range 0.03 months to 14.49 months). The majority of patients (61.7%) recovered from the eye disorder events.
Laboratory Abnormalities: The following table provides treatment-emergent shifts from baseline in laboratory abnormalities occurring in patients treated with ROZLYTREK across the 4 clinical trials. (See Table 14.)
Click on icon to see table/diagram/imagePostmarketing Experience: Not applicable.
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