LVEF schedule of Between days 15 Between days 15 Every 9 weeks assessments and 21 of cycles 2, and 21 of Cycles 2, during study 4, 8, 11 and 15, 4 and 6, after treatment, at the and surgery, surgery and < 7 treatment and < 7 days prior days prior to cycle discontinuation to cycle 5, and 7, and between visit, then every 6 after cycle 17 and days 15 and 21 of months for the 21 (Ptz + D arm cycles 10, 12 and first year, then only) (that is, 15 and 18 annually for up to every 6 weeks (FEC/Ptz + T + D 3 years after the during arm only) (that is, treatment neoadjuvant and every 6 weeks discontinuation adjuvant therapy). during the visit Subsequent LVEF neoadjuvant assessments every period and every 6 months for 2 6-9 weeks during years the adjuvant period), at the post-treatment visit, then every 6 months for 2 years, then annually for 2 years Central review of Safety data (in Copies of MUGA An independent cardiac data general) reviewed and ECHO Cardiac Review by steering recordings were Committee (CRC) committee sent to a central reviewed data for laboratory 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: 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 33. 33: Other events to monitor in the NEOSPHERE (WO20697), TRYPHAENA (BO22280) and CLEOPATRA (WO20698) studies (17, 22, 23) Adverse events to monitor Safety analysis strategy
LVEF schedule of assessments Between days 15 and 21 of cycles 2, 4, 8, 11 and 15, and 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, after 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 6-9 weeks during the adjuvant period), at the post-treatment visit, then every 6 months for 2 years, then annually for 2 years Every 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: 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 33. 33: Other events to monitor in the NEOSPHERE (WO20697), TRYPHAENA (BO22280) and CLEOPATRA (WO20698) studies (17, 22, 23) Adverse events to monitor Safety analysis strategy
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