Prophylactic use of pegfilgrastim enables the management of severe neutropenia without dose delays in patients with metastatic colorectal cancer treated with TAS‑102 plus bevacizumab

Abstract

Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal cancer (mCRC); however, this treatment is associated with an increased frequency of severe neutropenia (number of neutrophils <1,000), which should ideally be managed without dose delays. The present study provided a retrospective review of 35 patients with mCRC, and aimed to elucidate the benefits of prophylactic pegfilgrastim for the treatment of severe neutropenia. Patients received TAS-102 (35 mg/m 2 ) orally twice daily on days 1-5 and 8-12 of each 28-day treatment cycle, along with intravenous bevacizumab (5 mg/kg) on days 1 and 15. Moreover, the patients received 3.6 mg pegfilgrastim on day 15 of each cycle. The incidence of adverse events (AEs), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were assessed. In the first and subsequent cycles, 23 and 12 patients, respectively, received pegfilgrastim. The most common AE experienced was grade 3/4 neutropenia (8 patients; 22.9%). Among these 8 patients, 6 (17.1%) and 3 (8.6%) exhibited neutropenia prior to receiving pegfilgrastim or following discontinuation of pegfilgrastim administration, respectively. Moreover, 1 individual among these 8 patients (2.9%) demonstrated grade 3 neutropenia both prior to receiving pegfilgrastim and following discontinuation of pegfilgrastim. A total of 2 patients (5.7%) exhibited grade 3 bone pain, which prevented sustainable administration of pegfilgrastim and resulted in grade 3 neutropenia. Dose delays and dose reduction of TAS-102 due to neutropenia were required in 5 (14.3%) and 2 (5.7%) patients, respectively, during the treatment period. None of the patients exhibited severe neutropenia during chemotherapy after pegfilgrastim administration, thereby preventing dose delays and dose reduction of TAS-102. The relative dose intensity was 96.8% (65.0-100.0%), and the DCR was 54.3%. The median PFS and median OS were 4.4 and 14.9 months, respectively. In conclusion, prophylactic pegfilgrastim may facilitate the management of severe neutropenia without dose delays in patients with mCRC treated with TAS-102 plus bevacizumab.

A Systematic Review and Meta-Analysis of Trifluridine/Tipiracil plus Bevacizumab for the Treatment of Metastatic Colorectal Cancer: Evidence from Real-World Series

“…The main types of identified articles leading to exclusion were reviews, guidelines, and editorials. Ten series for potential inclusion in the meta-analysis were identified [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. After evaluation, two of the series were excluded, as they contained, based on the authors, similar centers and dates of study performance, potentially overlapping patients [ 26 , 27 ].…”

“…After evaluation, two of the series were excluded, as they contained, based on the authors, similar centers and dates of study performance, potentially overlapping patients [ 26 , 27 ]. Among the remaining eight series, six series were from Asia (of which five series were from Japan, where trifluridine/tipiracil was initially developed, and one series from China, Table 1 ) [ 18 , 21 , 22 , 23 , 24 , 25 ]. Two series were from European centers [ 19 , 20 ].…”

“…This difference was not statistically significant. The other western study and the three Asian studies, that included data on the number of previous lines of therapies, did not report efficacy results according to the number of previous lines of treatment received [ 18 , 20 , 21 , 22 ]. Similarly, no data on efficacy of treatment, according to whether patients had undergone surgery for the primary site, were reported.…”