P-240 Frequency and Management of Trifluridine/tipiracil (FTD/TPI) + Bevacizumab (Bev)-Associated Neutropenia in Patients with Refractory Metastatic Colorectal Cancer (mcrc) in Real-World Practice

In the Sunlight study, the combination of FTD/TPI+ BEV was associated with a statistically and clinically significant overall survival benefit, with neutropenia being the most frequent adverse event. However, we do not know its frequency in routine clinical practice and we lack a protocol for its management. We conducted a retrospective, observational study of patients (pts) with mCRC refractory or intolerant to standard therapies treated with FTD/TPI 35 mg/m2 twice daily on days 1–5 and 8–12 every 28 days plus BEV 5 mg/kg on days 1 and 15 every 28 days at University Hospital Complex of A Coruña (Spain). Patients with reduced initial dose (N=8) or prophylactic use of G-CSF (N=6) were excluded. We recorded 48 pts. treated between July 2019 to December 2022. Median age was 66.4 years (range 44 – 82), 83.3% ECOG PS0-1, 41.7% >3 metastatic locations, 72.9% liver metastases, 27.1% time since diagnosis of 1st metastases < 18 months and 54.2% poor prognostic Tabernero subgroup. Previous treatment included 91.7% antiVEGF and 83.3% received FTD/TPI + BEV as 3rd line of treatment. Median of cycles received was 4 (range 1-19+). ORR and DCR were 2.2% and 48.9%, respectively. With a median follow up of 13 months, median PFS was 4.3 months (95% CI, 3.4-5.2 months) and median OS was 11.1 months (95% CI, 8.7-13.6 months). The most frequent treatment-related adverse events were: neutropenia (all grades 91.7%, grade 2 27.1%, grade 3 45.8%, grade 4 12.5% and febrile neutropenia 0%), asthenia (all grades 60.4%, grade 2 16.7% and grade 3 12.5%) and anaemia (all grades 56.2%, grade 2 18.8% and grade 3 2.1%). Neutropenia appeared mainly during the first 3 cycles of treatment (cycle 1 29.5%, cycle 2 45.5%, cycle 3 15.9% and cycle 4+ 9.1%); and neutropenia was managed with dose reduction (12.2%), G-CSF (48.8%), dose reduction + G-CSF (7.3%) or no management (31.7%); when patient did not receive further treatment due to disease progression. G-CSF used was filgastrim (30.4%), 3 or 5 injections between days 14 and 18; or pegfilgastrim (69.6%), single dose on day 15 (coinciding with bevacizumab administration). Our series confirms that neutropenia is the most frequent adverse event in the context of routine clinical practice. We propose a management protocol for FTD/TPI + BEV-associated neutropenia, based on the presence of other concomitant adverse events; using G-CSF (filgastrim 3-5 doses between days 14 and 18 or pegfilgastrim single dose day 15) for the management of isolated neutropenia and dose reduction in the presence of other significant adverse events.