b'Prescribing Information]. Patients received LONSURF 35 mg/m2/doseIndian or Alaska Native, and 9.6% were unknown; and baseline ECOG (n=533) or placebo (n=265) twice daily on Days 1 through 5 and Days 8performance status 0 (46%), 1 (54%), or 2 (0.2%).through 12 of each 28-day cycle. In RECOURSE, 12% of patients receivedSerious adverse reactions occurred in 25% of patients. The most frequent LONSURF for more than 6 months and 1% of patients received LONSURFserious adverse reactions (2%) were intestinal obstruction (2.8%), and for more than 1 year. COVID-19 (2%). Fatal adverse reactions occurred in 1.2% of patients who The study population characteristics were: median age 63 years; 61% male;received LONSURF in combination with bevacizumab, including rectal fistula 57% White, 35% Asian, and 1% Black.(0.4%), bowel perforation (0.4%) and atrial fibrillation (0.4%).The most common adverse reactions or laboratory abnormalities (10% in Permanent treatment discontinuation due to an adverse reaction occurred incidence) in patients treated with LONSURF at a rate that exceeds the rate in 13% of patients. The adverse reaction which resulted in permanent in patients receiving placebo were anemia, neutropenia, asthenia/fatigue,treatment discontinuation in 2% of patients was fatigue.nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting,Dosage reductions due to an adverse reaction or laboratory abnormality abdominal pain, and pyrexia. occurred in 7% of patients. At least one dose reduction in 3.7% of patients In RECOURSE, 3.6% of patients discontinued LONSURF for an adversewas required for neutropenia.reaction and 14% of patients required a dose reduction. The most commonDosage interruptions due to an adverse reaction occurred in 11% of patients adverse reactions or laboratory abnormalities leading to dose reduction werewho received LONSURF in combination with bevacizumab. The adverse neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.reaction that required dosage interruption in 2% of patients was nausea.Table 3 and Table 4 list the adverse reactions and laboratory abnormalitiesThe most common adverse reactions or laboratory abnormalities (20% (graded using CTCAEv4.03), respectively, observed in RECOURSE.in incidence) in patients treated with LONSURF in combination with Table 3Adverse Reactions (5%) in Patients Receiving LONSURF andbevacizumab were neutropenia, anemia, thrombocytopenia, fatigue, nausea,at a Higher Incidence (2%) than in Patients Receiving Placeboincreased aspartate aminotransferase, increased alanine aminotransferase, in RECOURSE increased alkaline phosphatase, decreased sodium, diarrhea, abdominal Adverse Reactions LONSURF Placebo pain, and decreased appetite. Table 5 and Table 6 list the adverse reactions (N=533) (N=265) and laboratory abnormalities, respectively, observed in SUNLIGHT.AllGradesAllGradesTable 5:Adverse Reactions (5%) in SUNLIGHTGrades 3-4* Grades 3-4* Adverse Reactions LONSURF +LONSURF (%) (%) (%) (%) BevacizumabGeneral(N=246) (N=246)Asthenia/fatigue 52 7 35 9 (%) (%)Pyrexia 19 1.3 14 0.4 AllGrade AllGradeGrades3 or 4Grades3 or 4GastrointestinalGastrointestinal disordersNausea 48 1.9 24 1.1 Nausea371.6271.6Diarrhea 32 3 12 0.4 Diarrhea*211.2192.4Vomiting 28 2.1 14 0.4 Abdominal pain*202.8183.7Abdominal pain 21 2.4 19 3.8 Vomiting*190.8151.6Stomatitis 8 0.4 6 0 Stomatitis*130.44.10Metabolism and nutrition Constipation110110.8Decreased appetite 39 3.6 29 4.9 General disorders and administration site conditionsInfections27 7 16 4.9 Fatigue*455378Nervous systemPyrexia4.9060.4Dysgeusia 7 0 2.3 0 Infections and Skin and subcutaneous tissueinfestations*318248Alopecia 7 0 1.1 0 Metabolism and nutrition disorders*No Grade 4 definition for nausea, abdominal pain, or fatigue in NationalDecreased appetite200.8151.2Cancer Institute Common Terminology Incidence reflects 64 preferred terms in the Infections and InfestationsMusculoskeletal and connective tissue disorderssystem organ class.Musculoskeletal pain*181.2112Table 4Laboratory Abnormalities in RECOURSE Nervous system disorderLaboratory Parameter* LONSURF Placebo Headache803.70AllGradesAllGradesVascular disordersGrades3-4Grades3-4Hypertension*11621.2(%) (%) (%) (%) Hemorrhage*101.23.70.8Hematologic Renal and urinary disordersAnemia 77 18 33 3 Proteinuria6 0.81.2 0Neutropenia67 38 0.8 0 *Represents a composite of multiple related terms Thrombocytopenia 42 5 8 0.4 Table 6: Select Laboratory Abnormalities (10%) in SUNLIGHT* Worst Grade at least one grade higher than baseline, with percentagesLONSURF + LONSURFabased on number of patients with post-baseline samples, which may beLaboratory parametersBevacizumaba 533 (LONSURF) or 265 (placebo) One Grade 4 anemia adverse reaction based on clinical criteria wasAll Grade All GradereportedGrades 3 or 4 Grades 3 or 4In RECOURSE, pulmonary emboli occurred more frequently in LONSURF- (%) (%) (%) (%)treated patients (2%) compared to no patients on placebo. HematologyLONSURF in combination with bevacizumab Neutrophils decreased80526839The safety of LONSURF in combination with bevacizumab was evaluated inHemoglobin decreased6857311SUNLIGHT, an international, randomized, open label study in patients with previously treated metastatic colorectal cancer [see Clinical Studies (14.1) Platelets decreased544.1290.8in the full Prescribing Information]. (continued)The study population characteristics were: median age 63 years (20 to90 years); 52% male; 88% White, 1.4% Black, 0.2% Asian, 0.2% American Taiho_Directory_USMed_Dec2023_FullAd_NAout_7.875x10.75_L09.indd 4 11/27/23 6:17 PM'