2.3. Adverse Events
death, treatment-emergent adverse, TEAEs, pain, treatment-emergent, bruising, deaths
ADVERSE EVENTS, DISEASE
All patients treated with regorafenib (N = 48) reported at least one AE, and a total of 818 AEs were reported. 760 AEs were treatment-emergent adverse events (TEAEs), with all patients (N = 48) experiencing at least one TEAE (see 542. TEAEs were deemed related (possibly, probably, or definitely) to regorafenib and were experienced by 47 (97.9%) out of 48 patients (Out of 760 TEAEs reported, a total of 85 (11.2%) and 14 (1.8%) were in Grade 3 and Grade 4, respectively. Most TEAEs reported were Grade 1 (443, 58.3%) and Grade 2 (174, 22.9%). Forty-four (44, 5.8%) TEAEs were graded as unknown. Two (4.2%) patients experienced only TEAE of Grade 1 severity. The highest severity of any TEAE experienced by 10 (20.8%), 29 (60.4%), and 7 (14.6%) patients was in Grade 2, Grade 3, and Grade 4, respectively. Thus, most patients experienced at least once a TEAE of Grade 3 (see The most frequently occurring Grade ≥3 TEAEs reported by maximum severity per patient are presented in A total of 19 serious adverse events (SAEs) were reported by 16 (33.3%) out of 48 patients who had received regorafenib. All SAEs were treatment-emergent (TESAE) (see Twenty-three (23) deaths were reported in electronic data capture (EDC). One death occurred before treatment initiation, while the other 22 occurred after treatment discontinuation. No deaths occurred within 13 days after the last dose administration and, thus, were not accounted for in the PFS analysis. The times of death from the time of treatment discontinuation are as follows: fourteen (14, 93.3%) out of the 15 deaths that occurred within first year of the last dose administered were due to the progression of the disease, and six (85.7%) out of the seven deaths that occurred after one year were due to the progression of the disease—the distribution of death time after treatment discontinuation is summarized in Metastatic biopsies were obtained from 37 (77.1%) out of the 48 patients treated with regorafenib before the initiation of study treatment. Biopsied lesions were collected from the liver, lung, lymph node, abdomen, or other locations. Seven (18.9%) patients out of the 37 biopsied-dosed patients reported a total of 8 AEs related to the biopsy that consisted of pain and/or bruising. None were considered serious; all were Grade 1 or 2, and none prevented the initiation of study treatment.