ions, 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 rate observed in practice.
The safety data described below, except where noted, are derived from a randomized (2:1), double-blind, placebo-controlled trial (Study 1) in which 500 patients (median age 61 years; 61% men) with previously treated metastatic colorectal cancer received Stivarga as a single agent at the dose of 160 mg daily for the first 3 weeks of each 4 week treatment cycle and 253 patients (median age 61 years; 60% men) received placebo. The mean duration of therapy was 12 weeks for patients receiving Stivarga and 8 weeks for patients receiving placebo. Due to adverse reactions, 61% of the patients receiving Stivarga required a dose interruption and 38% of the patients had their dose reduced. Drug-related adverse reactions that resulted in treatment discontinuation were reported in 8.2% of Stivarga-treated patients compared to 1.2% of patients who received placebo. Skin toxicity (HFSR/PPE or rash) was the most common cause of permanent drug discontinuation.
The most frequently observed adverse drug reactions (≥30%) in patients receiving Stivarga are asthenia/fatigue, decreased appetite and food intake, HFSR/PPE, diarrhea, mucositis, weight loss, infection, hypertension and dysphonia.
The most serious adverse drug reactions in patients receiving Stivarga are hepatotoxicity, hemorrhage, and gastrointestinal perforation.
Table 1compares the incidence of adverse reactions (≥10%) in patients receiving Stivarga and reported more commonly than in patients receiving placebo (Study 1).
Table 1: Adverse drug reactions (≥10%) reported in patients treated with Stivarga and reported more commonly than in patients receiving placebo
Other adverse reactions observed more commonly in patients treated with Stivarga than placebo and that occurred in <10% (all grades) were: dry skin (8.8 vs. 3.2), proteinuria (8.6 vs. 2.4), alopecia (7.6 vs. 1.6), hypokalemia (7.6 vs. 1.9), taste disorder (7.6 vs. 2.4), increase in transaminases (7.6 vs. 4.4), hypophosphatemia (6.4 vs. 0.8), increase in lipase (6.2 vs. 1.2), musculoskeletal stiffness (6.0 vs. 2.0), hypocalcemia (5.8 vs. 0.4), hyponatremia (5.8 vs. 2.4), dry mouth (4.8 vs. 2.0), leukopenia (4.2 vs. 0.8), hypothyroidism (4.2 vs. 0.4), increase in amylase (3.0 vs. 0.4), abnormal international normalized ratio (INR) (2.4 vs. 0.8), hypomagnesemia (2.2 vs. 0.4), tremor (2.0 vs. 0.0), gastroesophageal reflux (1.4 vs. 0.0), hyperuricemia (1.2 vs. 0.0), gastroenteritis (1.2 vs. 0.4), nail disorder (1.0 vs. 0.0), gastrointestinal fistula (0.8 vs. 0.4), myocardial ischemia (0.6 vs. 0.4), myocardial infarction (0.4 vs. 0.0).
Other adverse reactions observed in patients treated with Stivarga in open-label or placebo-controlled clinical trials (more than 1100 Stivarga treated patients) were: gastrointestinal perforation (0.61%), severe liver injury*° (0.27%), hypertensive crisis (0.18%), reversible posterior leukoencephalopathy syndrome (RPLS) (0.09%), and keratoacanthoma/squamous cell carcinoma of the skin (0.09%).
Table 1: Adverse drug reactions (≥10%) reported in patients treated with Stivarga and reported more commonly than in patients receiving placebo
Adverse Reactions
Stivarga
(n=5 |
