Analysis of PFS

CovariateMedian PFS, months (95% CI)Univariate analysisMultivariate analysis
HR (95% CI)P valueHR (95% CI)P value
Age
- < 70 years (N = 105)7.0 (4.3–9.6)1.00-1.00-
- ≥ 70 years (N = 111)7.6 (6.2–9.1)0.83 (0.61–1.13)0.2400.81 (0.57–1.16)0.260
Sex
- Female (N = 74)7.7 (4.2–11.3)1.00-1.00-
- Male (N = 142)7.2 (5.6–8.8)0.78 (0.54–1.07)0.1300.78 (0.54–1.13)0.200
ECOG PS
- 0–1 (N = 175)8.1 (6.7–9.5)1.00-1.00-
- 2 (N = 41)3.3 (2.5–4.1)1.29 (0.86–1.92)0.2101.08 (0.68–1.72)0.734
Histologic subtype
- Nonsquamous (N = 167)6.7 (4.4–8.9)1.00-1.00-
- Squamous (N = 49)13.2 (4.9–21.5)0.60 (0.40–0.90)0.0150.45 (0.27–0.75)0.003
No. of metastatic sites
- ≤ 2 (N = 120)8.6 (5.4–11.7)1.00-1.00-
- > 2 (N = 96)4.3 (1.2–7.4)1.50 (1.10–2.05)0.0102.04 (1.15–3.61)0.014
Bone metastasis
- No (N = 172)8.1 (6.7–9.5)1.00-1.00-
- Yes (N = 44)3.4 (1.9–5.0)1.68 (1.16–2.43)0.0060.94 (0.57–1.55)0.833
Brain metastasis
- No (N = 161)7.5 (5.8–9.3)1.00-1.00-
- Yes (N = 55)7.0 (2.5–11.5)1.01 (0.71–1.44)0.9430.50 (0.29–0.86)0.013
Liver metastasis
- No (N = 196)7.7 (6.3–9.0)1.00-1.00-
- Yes (N = 20)3.4 (2.3–4.5)1.39 (0.83–2.30)0.2011.08 (0.58–2.00)0.794
PD-L1 TPS
- < 1% (N = 71)8.1 (7.0–9.2)1.00-1.00-
- ≥ 1% and ≤ 49% (N = 22)8.5 (2.9–14.2)1.07 (0.61–1.86)0.7991.95 (1.03–3.69)0.039
- ≥ 50% (N = 123)6.6 (4.5–8.7)1.04 (0.73–1.48)0.8062.99 (0.35–25.32)0.315
BMI
- < 25 kg/m2 (N = 102)5.4 (2.4–8.3)1.00-1.00-
- ≥ 25 kg/m2 (N = 114)9.7 (6.6–12.9)0.61 (0.45–0.84)0.0030.75 (0.52–1.08)0.130
Smoking habits
- Never (N = 20)3.4 (2.0–4.8)1.00-1.00-
- Ever (N = 196)7.7 (6.3–9.2)0.44 (0.27–0.72)0.0010.93 (0.52–1.67)0.818
Previous thoracic RT
- No (N = 188)7.2 (5.2–9.2)1.00-1.00-
- Yes (N = 28)7.7 (1.5–14.8)0.78 (0.50–1.23)0.2940.63 (0.38–1.04)0.073
LIPI score
- 0 (N = 84)24.5 (17.4–31.5)1.00-1.00-
- 1 (N = 68)6.2 (4.9–7.5)8.56 (5.04–14.53)< 0.00110.07 (5.69–17.83)< 0.001
- 2 (N = 64)2.3 (1.9–2.7)33.90 (18.76–61.27)< 0.00147.56 (24.75–91.38)< 0.001
First-line therapy
- Only pembrolizumab (N = 124)6.3 (1.1–8.4)1.00-1.00-
- Pemetrexed-based (N = 75)8.1 (6.3–9.9)0.99 (0.71–1.39)0.9811.91 (0.22–16.30)0.553
- Paclitaxel-based (N = 17)8.5 (6.6–10.5)0.76 (0.38–1.52)0.4482.00 (0.21–18.87)0.543
Corticosteroidsa
- No (N = 122)10.0 (7.4–12.7)1.00-1.00-
- Yes (N = 94)4.1 (2.6–5.6)1.79 (1.31–2.45)< 0.0011.59 (1.08–2.34)0.018
APAPb
- No (N = 154)8.9 (6.8–10.9)1.00-1.00-
- Yes (N = 62)3.4 (1.9–5.2)1.50 (1.07–2.11)0.0161.74 (1.17–2.59)0.006
Systemic antibioticsc
- No (N = 176)8.3 (6.5–10.1)1.00-1.00-
- Yes (N = 40)3.7 (2.9–4.5)1.70 (1.16–2.51)0.0071.42 (0.88–2.31)0.148
PPId
- No (N = 158)7.0 (5.5–8.5)1.00-1.00-
- Yes (N = 58)7.7 (3.8–11.7)1.01 (0.70–1.41)0.9980.92 (0.68–1.51)0.921
Benzodiazepines (generic intake)
- No (N = 108)5.7 (3.4–8.0)1.00-1.00-
- Yes (N = 108)8.1 (6.4–9.7)0.92 (0.68–1.26)0.6400.73 (0.52–1.01)0.063
Benzodiazepines (specific intake)
- No (N = 108)5.7 (3.4–8.0)1.00-1.00-
- N-unsubstituted (N = 51)6.7 (4.1–9.2)1.31 (0.88–1.94)0.1731.21 (0.77–1.89)0.402
- N-substituted (N = 57)9.7 (4.1–15.4)0.73 (0.50–0.97)0.0410.52 (0.34–0.79)0.002

PFS: progression-free survival; CI: confidence interval; HR: hazard ratio; ECOG PS: Eastern Cooperative Oncology Group Performance Status; PD-L1 TPS: programmed cell death ligand-1 tumor proportion score; BMI: body mass index; RT: radiotherapy; LIPI: lung immune prognostic index; APAP: acetaminophen; PPI: proton pump inhibitors. a Corticosteroids refer to the use of prednisone or an equivalent drug at a dose of at least 10 mg per day for at least 5 days within the 30 days before the start of treatment, excluding premedication for chemotherapy); b APAP refers to the use of at least 1,000 mg per day for more than 24 h during the 30 days before the start of treatment; c systemic antibiotics and d PPI refer to the use of these medications in the 30 days before the start of treatment