Comparison of prophylactic effects for chemotherapy-induced neutropenia between same-day versus next-day administration of pegteograstim in chemotherapy regimen composed of day 1 intensive myleosuppressive agent: A randomized clinical trial (CONCISE,

12126 Background: Same-day administration of pegylated G-CSF is frequently used in clinical practice despite guideline recommendations favoring next-day administration. This study evaluated whether same-day administration of pegteograstim is noninferior to next-day administration with respect to the duration of grade (Gr) 4 chemotherapy induced neutropenia (CIN) in multi-day regimens containing day 1-intensive myelosuppressive agents. Methods: This multicenter, open-label, randomized, noninferiority trial (originally designed as a phase III study) enrolled patients receiving adjuvant/neoadjuvant or first-line palliative chemotherapy, including mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX. Patients were assigned in a 1:1 ratio to receive pegteograstim 6mg either within 4 hours after completion of chemotherapy (same-day group) or 24-36 hours (next-day group). The primary endpoint was Gr 4 CIN duration during cycle 1 (C1). A total sample size of 160 patients was calculated to verify noninferiority with a margin of 0.6 days; however, the trial closed prematurely after enrolling 90 patients. Results: Of the 90 enrolled patients, 81 were included in the analyses (37 same-day, 44 next-day). Mean Gr4 CIN duration was 0.43 days (95% CI, 0.13–0.74) in the same-day group and 0.09 days (95% CI, 0.00–0.29) in the Next-day group. The mean difference (Same-day minus Next-day) was 0.342 days (90% CI, 0.037 - 0.646). Because the upper bound exceeded the prespecified noninferiority margin of 0.6 days, noninferiority was not demonstrated (p-value = 0.080 for noninferiority). The incidence of Gr4 CIN was 21.1% (8 patients) of same-day group and 2.3% (1 patient) in the next-day group. During cycles 1-4, febrile neutropenia occurred in 1 patient (2.6%) in the same-day group and 3 patients (6.8%) in the next-day group. Two deaths occurred in each group: one FN-related death occurred in the same-day group. Conclusions: Same-day administration of pegteograstim did not meet the prespecified criterion for noninferiority compared with next-day administration. The incidence of grade 4 CIN, a key secondary outcome, favored next-day administration. These randomized data support maintaining next-day pegteograstim as standard practice in multi-day regimens with day 1–intensive myelosuppression. Clinical trial information: KCT0007694.