Table 3 Univariate and multivariate logistic regression analyses of the risk factors associated with (A) treatment reduction from the second course and (B) febrile neutropenia incidence at the first course of DOC + RAM treatment.

(A)	Univariate analysis		Multivariate analysis
(A)	Odds ratio (95% CI)	P-value	Odds ratio (95% CI)	P-value
Sex
Male/female	0.85 (0.40–1.81)	0.67	Excluded	–
Age (years)
≥ 65/ < 65	1.43 (0.69–2.95)	0.34	Excluded	–
ECOG performance status
0–1/2	2.45 (0.29–20.62)	0.41	Excluded	–
Clinical stage
IV/recurrence	0.67 (0.28–1.58)	0.36	Excluded	–
Histology
Adenocarcinoma/others	0.77 (0.29–2.03)	0.60	Excluded	–
Liver metastasis existence
Present/absent	0.82 (0.28–2.40)	0.72	Excluded	–
BSA (m²)
≥ 1.6/< 1.6	1.03 (0.49–2.17)	0.93	Excluded	–
Neutropenia
Present/absent	0.34 (0.04–2.83)	0.32	Excluded	–
Anemia
Present/absent	0.25 (0.12–0.52)	0.0003**	0.29 (0.12–0.66)	0.004**
Thrombopenia
Present/absent	1.25 (0.31–5.09)	0.75	Excluded	–
Liver dysfunction
Present/absent	1.37 (0.60–3.11)	0.46	Excluded	–
Renal dysfunction
Present/absent	1.09 (0.47–2.51)	0.85	Excluded	–
Hypoalbuminemia
Present/absent	0.54 (0.26–1.15)	0.11	0.89 (0.37–2.11)	0.79
Smoking history
Current or former/never	0.49 (0.21–1.13)	0.09	0.46 (0.18–1.20)	0.11
Alcohol intake (≥ 5 days in a week)
Present/absent	0.63 (0.30–1.33)	0.22	Excluded	–
Treatment line
Second-line/third- or later-line	1.04 (0.50–2.17)	0.92	Excluded	–
Number of prior cytotoxic regimens
0–1/2 or more	1.23 (0.51–2.98)	0.65	Excluded	–
ICI treatment history
Present/absent	0.63 (0.31–1.31)	0.22	Excluded	–
Dose reduction from initiation
Present/absent	0.70 (0.14–3.46)	0.67	Excluded	–
Prophylactic G-CSF administration
Present/absent	0.19 (0.09–0.40)	< 0.0001**	0.18 (0.08–0.42)	< 0.0001**

(B)	Univariate analysis		Multivariate analysis
(B)	Odds ratio (95% CI)	P-value	Odds ratio (95% CI)	P-value
Sex
Male/female	1.36 (0.53–3.48)	0.52	Excluded	–
Age (years)
≥ 65/< 65	0.79 (0.34–1.85)	0.59	Excluded	–
ECOG performance status
0–1/2	1.29 (0.15–11.03)	0.82	Excluded	–
Clinical stage
IV/recurrence	1.06 (0.37–3.08)	0.91	Excluded	–
Histology
Adenocarcinoma/others	0.96 (0.30–3.09)	0.94	Excluded	–
Liver metastasis existence
Present/absent	1.12 (0.35–3.63)	0.85	Excluded	–
BSA (m²)
≥ 1.6/< 1.6	1.83 (0.72–4.67)	0.20	Excluded	–
Neutropenia
Present/absent	0.61 (0.07–5.06)	0.64	Excluded	–
Anemia
Present/absent	0.22 (0.09–0.54)	0.0009**	0.22 (0.07–0.65)	0.006**
Thrombopenia
Present/absent	1.26 (0.25–6.31)	0.78	Excluded	–
Liver dysfunction
Present/absent	1.60 (0.63–4.07)	0.32	Excluded	–
Renal dysfunction
Present/absent	1.53 (0.60–3.88)	0.37	Excluded	–
Hypoalbuminemia
Present/absent	0.49 (0.21–1.15)	0.10	0.88 (0.30–2.60)	0.81
Smoking history
Current or former/never	1.15 (0.49–2.69)	0.74	Excluded	–
Alcohol intake (≥ 5 days in a week)
Present/absent	0.63 (0.30–1.33)	0.22	Excluded	–
Treatment line
Second-line/third- or later-line	1.16 (0.49–2.72)	0.74	Excluded	–
Number of prior cytotoxic regimens
0–1/2 or more	0.75 (0.29–1.97)	0.56	Excluded	–
ICI treatment history
Present/absent	0.66 (0.28–1.54)	0.34	Excluded	–
Dose reduction from initiation
Present/absent	Enable to calculate	–	Excluded	–
Prophylactic G-CSF administration
Present/absent	0.05 (0.02–0.15)	< 0.0001**	0.05 (0.01–0.16)	< 0.0001**

Liver dysfunction: grade 1 or higher aspartate aminotransferase, alanine aminotransferase, or total bilirubin elevation.
Renal dysfunction: creatinine clearance of < 60 mL/min.
CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; BSA, body surface area; ICI, immune checkpoint inhibitor; G-CSF, granulocyte colony-stimulating factor.
**P < 0.01.

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