Pegfilgrastim in colorectal cancer (CRC) patients (pts) receiving every-two-week (Q2W) chemotherapy (CT): Long-term results from a phase II, randomized, controlled study

Abstract

4072 Background: Survival in advanced CRC is prolonged by adding oxaliplatin (Ox) and/or irinotecan (Iri) to Q2W 5-fluorouracil/leucovorin (5FU/LV). Combination therapy, however, has a higher incidence of febrile neutropenia (FN) and related toxicities. This study evaluated pegfilgrastim dosing on day 4 of Q2W regimens in CRC. Here we present long-term follow-up of these pts. Methods: Advanced CRC pts were randomized (1:1) to pegfilgrastim 6mg or placebo, which was stratified by CT regimen received: FOIL, FOLFOX, or FOLFIRI. We previously reported grade 3/4 neutropenia (primary endpoint) in 43% placebo and 13% pegfilgrastim pts in the 4-cycle treatment phase (odds ratio = 0.19, 95% CI: 0.10–0.37; p < 0.0001). After end of treatment, pts were followed long term for ≤ 2 years (inclusive of ≤ 8 additional cycles) for serious adverse events (SAEs), overall survival (OS), and progression-free survival (PFS). Median follow-up time was 519 days. Kaplan-Meier methods estimated OS and PFS from study day 1. The study was not powered to detect PFS or OS differences between treatment groups. Results: Of 241 pts analyzed (123 pegfilgrastim, 118 placebo), 49% received FOLFOX, 26% FOLFIRI, and 25% FOIL. In the treatment period, 8% placebo and 2% pegfilgrastim pts had grade 3/4 FN ( Table ). Pegfilgrastim was well tolerated with no dose delays attributed to leukocytosis. Pegfilgrastim and placebo had similar PFS and OS ( Table ). No SAEs related to study drug were reported in the follow-up period. Conclusions: In this randomized, placebo-controlled study, pegfilgrastim significantly lowered neutropenic risk. Bone pain incidence in this CRC population was lower than in breast cancer pts treated with a taxane (Vogel J Clin Oncol 2005); the incidence in pegfilgrastim pts was modestly increased over placebo. Leukocytosis was not a concern despite the 11-day dosing interval. Long-term results suggest similar PFS and OS in the pegfilgrastim and placebo pts in this CRC study. [Table: see text] [Table: see text]