Timely G-CSF Administration Is Key for Hematologic AE Management in mPDAC Receiving NALIRIFOX

G-CSF in mPDAC Receiving NALIRIFOX

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A higher incidence of hematologic adverse effects (AEs) and use of granulocyte colony-stimulating factor (G-CSF) was noted among patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who were treated with NALIRIFOX (liposomal irinotecan, oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) and experienced longer overall survival (OS), according to findings from a post hoc analysis of the phase 3 NAPOLI 3 trial (NCT04083235).1

Findings presented at the 50th Annual Oncology Nursing Society (ONS) Congress showed that 45.8% of patients enrolled in North American centers (ITT population; n = 120) achieved an OS greater than 12 months (n = 55) and 54.2% of those who had an OS of 12 months or less (n = 65). Within these respective subgroups, the median OS was 18.4 months (95% CI, 15.44-not reached) and 5.9 months (95% CI, 4.86-7.62).

Within the safety population (n = 112), hematologic AEs occurred in 40.0% vs 28.1% of patients who achieved an OS greater than 12 months vs an OS lasting no more than 12 months, respectively. These effects included any-grade neutropenia (14.5% in > 12-month OS group; 10.5% in ≤ 12-month OS group), thrombocytopenia (10.9%; 7.0%), and anemia (25.5%; 21.1%). Notably, grade 1 (25.0%; 16.7%), 2 (12.5%; 50.0%), 3 (62.5%; 16.7%) and 4 (0.0%; 16.7%) neutropenic events were reported.

Overall, 36.6% of patients in the ITT population also received G-CSF, with 28.6% receiving it as prophylaxis, 16.1% as treatment, and 8.0% receiving both. Among patients who achieved an OS greater than 12 months, 47.3% received G-CSF—40% as prophylaxis and 18.2% as treatment. In comparison, 26.3% of patients who achieved an OS of 12 months or less received G-CSF; 17.5% and 14.0% of patients received the therapy as prophylaxis or treatment, respectively.

Furthermore, the mean incidence of G-CSF events per patient was higher in the greater than 12 months OS group than the 12-months or less OS group, (1.1 [SD ±2.8] vs 0.4 [SD ±0.8]). This included more prophylactic events (0.8 [SD ±2.3] vs 0.2 [SD ±0.6]) and a modest increase in treatment events (0.3 [SD ±0.8] vs 0.2 [SD ±0.5]).

“Oncology nurses play a key role in triaging, assessing and mitigating neutropenia post-infusion,” presenting author Keeran Sampat, MD, a medical oncologist at Virginia Cancer Specialists in Arlington, and coauthors wrote in a poster presentation of the data. “Ensuring that patients who are symptomatic receive G-CSF as soon as possible may keep patients on infusion schedules for longer and ultimately improve survival outcomes.”

The randomized, open-label, phase 3 NAPOLI trial was conducted at 187 sites across 18 countries and enrolled 770 patients aged 18 years or older with histologically or cytologically confirmed PDAC not previously treated in the metastatic setting. Eligible patients had an ECOG performance status (PS) of 0 or 1, confirmed metastatic disease diagnosed within 6 weeks of screening, and at least 1 measurable metastatic lesion per RECIST v1.1.

Patients were stratified according to ECOG PS, region, and the presence of liver metastases. They were randomly assigned 1:1 to receive either NALIRIFOX—comprising liposomal irinotecan at 50 mg/m², 5-FU at 2400 mg/m², leucovorin at 400 mg/m², and oxaliplatin at 60 mg/m² on days 1 and 15 of each 28-day cycle—or gemcitabine at 1000 mg/m² plus nab-paclitaxel (Abraxane) at 125 mg/m² on days 1, 8, and 15 of each cycle. Tumor assessments were performed every 8 weeks according to RECIST v1.1, and treatment was continued until disease progression, unacceptable toxicity, or withdrawal from the study. Follow-up was conducted every 8 weeks until death or study cessation.

G-CSF use was permitted at the investigator’s discretion for the management of febrile neutropenia or neutropenia-associated infections, as well as the prevention of febrile neutropenia in patients with an absolute neutrophil count of less than 500 cells/µL. Prophylactic use of G-CSF according to investigator’s discretion was also allowed for patients deemed at high risk for developing febrile neutropenia.

In February 2024, the FDA approved NALIRIFOX for the first-line treatment of patients with metastatic pancreatic adenocarcinoma based on previously reported data from NAPOLI 3.2

This exploratory post hoc analysis of NAPOLI 3 examined the occurrence of hematological AEs and utilization of G-CSF as a management strategy among patients from North America who received NALIRIFOX in NAPOLI 3 (ITT population).1

The median age was 65 years in both the 12-month OS or less subgroup (IQR, 53.5-69.0) vs the greater than 12-month OS subgroup (IQR, 60.0-71.0). A total of 36.9% and 45.5% of patients in these respective subgroups were female. The majority of patients across both subgroups were White (86.2% in ≤ 12-month OS group; 78.2% in > 12-month OS group), had an ECOG PS of 1 (69.2%; 52.7%), and had liver metastases (86.2%; 69.1%). Most patients in the 12-month or less OS subgroup had 2 metastatic sites (36.9%), followed by 3 or more sites (30.8%), and 1 site (32.3%). Conversely, in the greater than 12-month OS subgroup, most patients had 3 or more metastatic sites (49.1%), followed by 2 sites (27.3%), and 1 site (23.6%)

Disclosures: Sampat reported no disclosures.

References

1. Sampat K, Cusnir M, Cockrum P, et al. Describing hematological adverse events (AEs) and utilization of granulocyte-colony stimulating factor (G-CSF) among patients receiving NALIRIFOX for metastatic pancreatic ductal adenocarcinoma (mPDAC). Presented at: 50th Annual Oncology Nursing Society Congress; April 9-13, 2025. Denver, Colorado. Abstract I13.
2. FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma. FDA. February 13, 2024. Accessed April 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-irinotecan-liposome-first-line-treatment-metastatic-pancreatic-adenocarcinoma