Analysis of PFS
| Covariate | Median PFS, months (95% CI) | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|
| HR (95% CI) | P value | HR (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) | 0.240 | 0.81 (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) | 0.130 | 0.78 (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) | 0.210 | 1.08 (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) | 0.015 | 0.45 (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) | 0.010 | 2.04 (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) | 0.006 | 0.94 (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) | 0.943 | 0.50 (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) | 0.201 | 1.08 (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) | 0.799 | 1.95 (1.03–3.69) | 0.039 |
| - ≥ 50% (N = 123) | 6.6 (4.5–8.7) | 1.04 (0.73–1.48) | 0.806 | 2.99 (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) | 0.003 | 0.75 (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) | 0.001 | 0.93 (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) | 0.294 | 0.63 (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) | < 0.001 | 10.07 (5.69–17.83) | < 0.001 |
| - 2 (N = 64) | 2.3 (1.9–2.7) | 33.90 (18.76–61.27) | < 0.001 | 47.56 (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) | 0.981 | 1.91 (0.22–16.30) | 0.553 |
| - Paclitaxel-based (N = 17) | 8.5 (6.6–10.5) | 0.76 (0.38–1.52) | 0.448 | 2.00 (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) | < 0.001 | 1.59 (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) | 0.016 | 1.74 (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) | 0.007 | 1.42 (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) | 0.998 | 0.92 (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) | 0.640 | 0.73 (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) | 0.173 | 1.21 (0.77–1.89) | 0.402 |
| - N-substituted (N = 57) | 9.7 (4.1–15.4) | 0.73 (0.50–0.97) | 0.041 | 0.52 (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