questionnaire eForm LVEF schedule of Between Days 15 Between Days 9 weeks assessments and 21 of Cycles 15 and 21 of during study 2, 4, 8, 11 and 15, Cycles 2, 4 and 6, treatment, at the and after surgery and treatment surgery, and < 7 7 days prior to discontinuation ≤ days prior to Cycle 7, and visit, then every Cycle 5, and after between Days 6 months for the Cycle 17 and 21 15 and 21 of first year, then (Ptz + D arm Cycles 10, 12 annually for up only) (that is, and 15 and 18 to 3 years after every 6 weeks (FEC/Ptz + T + D the treatment during arm only) (that discontinuation neoadjuvant and is, every 6 weeks visit adjuvant during the therapy). neoadjuvant Subsequent LVEF period and every assessments 6 to 9 weeks every 6 months during the for 2 years adjuvant period), at the post-treatment visit, then every 6 months for 2 years, then annually for 2 years Central review Safety data (in Copies of MUGA An independent of cardiac data general) and ECHO Cardiac Review reviewed by recordings were Committee (CRC) steering sent to a central reviewed data committee laboratory for for all potential independent cardiac events assessment CHF= congestive heart failure; LVEF = left ventricular ejection fraction; LVSD = left ventricular systolic dysfunction; NCI-CTCAE= National Cancer Institute Common Terminology Criteria for Adverse Events; NYHA = New York Heart Association Comment: There was some variability in the terminology used to describe significant cardiac dysfunction, with symptomatic left ventricular systolic dysfunction (Grade 3 and above) being used in the TRYPHAENA (BO22280) and CLEOPATRA (WO20698) studies and symptomatic LVSD being classified as congestive heart failure in the NEOSPHERE (WO20697) study. This is considered in reviewing the aggregate data across the studies. Several other parameters were specifically followed as per Table 4. Table 4: Other events to monitor in the NEOSPHERE (WO20697), TRYPHAENA (BO22280) and CLEOPATRA (WO20698) studies (17, 22 and 23) Adverse events to monitor Safety analysis strategy
questionnaire eForm LVEF schedule of assessments Between Days 15 and 21 of Cycles 2, 4, 8, 11 and 15, and after surgery, and < 7 days prior to Cycle 5, and after Cycle 17 and 21 (Ptz + D arm only) (that is, every 6 weeks during neoadjuvant and adjuvant therapy). Subsequent LVEF assessments every 6 months for 2 years Between Days 15 and 21 of Cycles 2, 4 and 6, surgery and ≤ 7 days prior to Cycle 7, and between Days 15 and 21 of Cycles 10, 12 and 15 and 18 (FEC/Ptz + T + D arm only) (that is, every 6 weeks during the neoadjuvant period and every 6 to 9 weeks during the adjuvant period), at the post-treatment visit, then every 6 months for 2 years, then annually for 2 years 9 weeks during study treatment, at the treatment discontinuation visit, then every 6 months for the first year, then annually for up to 3 years after the treatment discontinuation visit Central review of cardiac data Safety data (in general) reviewed by steering committee Copies of MUGA and ECHO recordings were sent to a central laboratory for independent assessment An independent Cardiac Review Committee (CRC) reviewed data for all potential cardiac events CHF= congestive heart failure; LVEF = left ventricular ejection fraction; LVSD = left ventricular systolic dysfunction; NCI-CTCAE= National Cancer Institute Common Terminology Criteria for Adverse Events; NYHA = New York Heart Association Comment: There was some variability in the terminology used to describe significant cardiac dysfunction, with symptomatic left ventricular systolic dysfunction (Grade 3 and above) being used in the TRYPHAENA (BO22280) and CLEOPATRA (WO20698) studies and symptomatic LVSD being classified as congestive heart failure in the NEOSPHERE (WO20697) study. This is considered in reviewing the aggregate data across the studies. Several other parameters were specifically followed as per Table 4. Table 4: Other events to monitor in the NEOSPHERE (WO20697), TRYPHAENA (BO22280) and CLEOPATRA (WO20698) studies (17, 22 and 23) Adverse events to monitor Safety analysis strategy
auspar-pertuzumab-160616.docx