G-CSF Prophylaxis Reduces Incidence of Febrile Neutropenia Without Compromising Chemoimmunotherapy Outcomes in Patients With Small Cell Lung Cancer

Clinical Summary:

• Design/Population: This multicenter, retrospective trial evaluated primary granulocyte colony-stimulating factor (G-CSF) prophylaxis in patients with extensive-stage or relapsed limited-stage small cell lung cancer (SCLC) receiving first-line platinum-etoposide plus atezolizumab or durvalumab. 
• Key Outcomes: Primary G-CSF prophylaxis significantly reduced the rate of febrile neutropenia, febrile neutropenia-related emergency visits and hospital admissions, and higher average relative dose intensity. No statistically significant differences in objective response, progression-free, or overall survival were observed between groups. 
• Clinical Relevance: These findings support consideration of primary G-CSF prophylaxis during first-line chemoimmunotherapy for SCLC, particularly in patients at elevated risk for febrile neutropenia, without evidence of compromised antitumor activity. However, the retrospective design limits casual conclusions, and prospective validation is needed.

According to results from the TORG-TG2504 trial, primary granulocyte colony-stimulating factor (G-CSF) prophylaxis was associated with significantly lower febrile neutropenia incidence and fewer febrile neutropenia-related emergency visits and hospital admissions among patients with small cell lung cancer (SCLC) receiving first-line chemoimmunotherapy. 

“Platinum-etoposide plus a programmed death-ligand 1 inhibitor is standard first-line therapy for extensive-stage SCLC… however febrile neutropenia is a frequent adverse event,” stated Shuhei Teranishi, MD, Kanagawa Cancer Center, Kanagawa, Japan, and coauthors. “Primary G-CSF prophylaxis may reduce febrile neutropenia but also modulate antitumor immunity.”

In this retrospective study, researchers collected data from patients with extensive-stage or recurrent limited-stage SCLC who received first-line platinum-etoposide plus atezolizumab or durvalumab between September 2019 and December 2023. 

Among the 285 patients enrolled, 64 received primary G-CSF prophylaxis, defined as administration of pegylated G-CSF during the first treatment cycle, while 221 did not receive primary prophylaxis.

Patients in the primary prophylaxis group received 3.6 mg of pegfilgrastim subcutaneously at least 24 hours after completing cytotoxic chemotherapy during cycle 1. The decision to administer prophylaxis was made by treating physicians according to routine clinical practice.

The primary end point was febrile neutropenia incidence during first-line treatment. Key secondary end points included febrile neutropenia-related emergency visits, hospitalizations, mortality, average relative dose intensity, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Investigators used inverse probability of treatment weighting to adjust for differences in baseline patient characteristics, with propensity score matching performed as a sensitivity analysis.

In the inverse probability of treatment weighting-adjusted analysis, febrile neutropenia occurred in 2.6% of patients receiving primary prophylaxis and 28.6% who did not receive primary prophylaxis (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02 to 0.3; P < .001). 

Febrile neutropenia-related emergency visits were also significantly less frequent among patients receiving primary prophylaxis, occurring in 1.6% and 16.1% of patients, respectively (OR, 0.09; 95% CI, 0.01 to 0.67; P = .02). 

Similarly, febrile neutropenia-related hospital admissions occurred in 1.6% of patients receiving primary prophylaxis and 15.3% of patients who did not receive primary prophylaxis (OR, 0.09; 95% CI, 0.01 to 0.71; P = .02). Febrile neutropenia-related mortality rates were 0% and 0.8%, respectively.

Among patients who completed all 4 cycles, average relative dose intensity was 0.76 in patients receiving primary prophylaxis and 0.71 in patients who did not did not receive primary prophylaxis (adjusted mean difference, 0.06; 95% CI, 0.01 to 0.1; P = .01). However, the proportion of patients completing all 4 cycles did not differ significantly between groups (77.8% vs 84.1%; P = .33).

Despite the reduction in febrile neutropenia incidence, no statistically significant differences in antitumor efficacy were observed between treatment groups. The ORR was 65.7% with primary prophylaxis and 73.1% without primary prophylaxis (OR, 0.71; 95% CI, 0.36 to 1.42; P = .33). 

Median PFS was 4.8 months with primary prophylaxis and 5.1 months without primary prophylaxis (HR, 0.88; 95% CI, 0.63 to 1.22; P = .44). Median OS was 14.2 months and 13.2 months, respectively (HR, 0.79; 95% CI, 0.55 to 1.13; P = .20).

Sensitivity analyses using propensity score matching demonstrated comparable findings, with significantly lower febrile neutropenia incidence among patients receiving primary prophylaxis and no statistically significant differences in ORR, PFS, or OS. 

However, differences in febrile neutropenia-related emergency visits, hospital admissions, and average relative dose intensity did not reach statistical significance in the propensity score-matched analyses. 

Grade ≥3 neutropenia occurred in 26.6% of patients receiving primary prophylaxis and 77.4% of patients without primary prophylaxis. Grade ≥3 leukopenia occurred in 25% and 62% of patients, respectively. 

Grade ≥3 thrombocytopenia occurred in 12.5% of patients receiving primary prophylaxis and 19% of patients without primary prophylaxis. Grade ≥3 anemia occurred in 7.8% and 10% of patients, respectively. 

“These findings support considering primary G-CSF prophylaxis, rather than withholding it solely because of theoretical immunologic concerns, particularly in settings where febrile neutropenia risk is high,” concluded Dr Teranishi et al. “However, prospective validation studies in more diverse populations are needed.”

Source:

Teranishi S, Misumi Y, Ishihara T, et al. Efficacy and safety of primary granulocyte colony-stimulating factor prophylaxis in patients with small-cell lung cancer receiving first-line platinum–etoposide plus a programmed death-ligand 1 inhibitor: A multicenter retrospective observational study. Lung Cancer. Published online: October 19, 2026. doi: 10.1016/j.lungcan.2026.109671