Analysis of OS
| Covariate | Median OS, months (95% CI) | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | ||
| Age | |||||
| - < 70 years (N = 105) | 13.3 (9.7–16.8) | 1.00 | - | 1.00 | - |
| - ≥ 70 years (N = 111) | 12.0 (8.7–15.2) | 0.86 (0.62–1.18) | 0.352 | 0.83 (0.57–1.23) | 0.369 |
| Sex | |||||
| - Female (N = 74) | 11.6 (6.4–16.8) | 1.00 | - | 1.00 | - |
| - Male (N = 142) | 13.3 (11.1–15.5) | 0.82 (0.59–1.13) | 0.235 | 0.79 (0.53–1.18) | 0.256 |
| ECOG PS | |||||
| - 0–1 (N = 175) | 13.4 (11.3–15.6) | 1.00 | - | 1.00 | - |
| - 2 (N = 41) | 7.3 (6.0–8.6) | 1.28 (0.84–1.93) | 0.239 | 1.09 (0.67–1.77) | 0.727 |
| Histologic subtype | |||||
| - Nonsquamous (N = 167) | 11.1 (7.9–14.2) | 1.00 | - | 1.00 | - |
| - Squamous (N = 49) | 14.8 (10.2–19.4) | 0.69 (0.46–1.04) | 0.082 | 0.65 (0.39–1.09) | 0.104 |
| No. of metastatic sites | |||||
| - ≤ 2 (N = 120) | 14.3 (13.1–15.5) | 1.00 | - | 1.00 | - |
| - > 2 (N = 96) | 9.1 (6.1–12.1) | 1.50 (1.09–2.07) | 0.013 | 3.19 (1.76–5.76) | < 0.001 |
| Bone metastasis | |||||
| - No (N = 172) | 13.4 (11.2–15.6) | 1.00 | - | 1.00 | - |
| - Yes (N = 44) | 9.0 (6.0–11.9) | 1.58 (1.08–2.33) | 0.018 | 0.72 (0.43–1.22) | 0.234 |
| Brain metastasis | |||||
| - No (N = 161) | 13.3 (11.3–15.4) | 1.00 | - | 1.00 | - |
| - Yes (N = 55) | 10.8 (4.3–17.3) | 0.96 (0.67–1.39) | 0.859 | 0.51 (0.30–0.86) | 0.012 |
| Liver metastasis | |||||
| - No (N = 196) | 13.0 (10.7–15.4) | 1.00 | - | 1.00 | - |
| - Yes (N = 20) | 10.4 (1.9–19.7) | 1.25 (0.74–2.11) | 0.391 | 0.51 (0.32–1.19) | 0.155 |
| PD-L1 TPS | |||||
| - < 1% (N = 71) | 12.0 (10.2–13.7) | 1.00 | - | 1.00 | - |
| - ≥ 1% and ≤ 49% (N = 22) | 14.7 (12.3–17.2) | 0.92 (0.64–1.33) | 0.684 | 1.57 (0.80–3.11) | 0.188 |
| - ≥ 50% (N = 123) | 9.9 (3.8–16.1) | 0.88 (0.50–1.52) | 0.651 | 1.83 (0.21–15.78) | 0.582 |
| BMI | |||||
| - < 25 kg/m2 (N = 102) | 9.9 (5.8–14.1) | 1.00 | - | 1.00 | - |
| - ≥ 25 kg/m2 (N = 114) | 13.7 (10.1–17.4) | 0.63 (0.46–0.87) | 0.006 | 0.69 (0.48–1.01) | 0.059 |
| Smoking habits | |||||
| - Never (N = 20) | 4.9 (2.3–7.4) | 1.00 | - | 1.00 | - |
| - Ever (N = 196) | 13.3 (11.0–15.5) | 0.58 (0.35–0.95) | 0.033 | 1.13 (0.62–2.04) | 0.679 |
| Previous thoracic RT | |||||
| - No (N = 188) | 11.6 (9.0–14.3) | 1.00 | - | 1.00 | - |
| - Yes (N = 28) | 16.1 (11.5–20.8) | 0.75 (0.47–1.18) | 0.214 | 0.37 (0.22–0.64) | < 0.001 |
| LIPI score | |||||
| - 0 (N = 84) | 28.4 (15.3–41.4) | 1.00 | - | 1.00 | - |
| - 1 (N = 68) | 11.0 (9.4–12.6) | 21.03 (11.25–39.30) | < 0.001 | 39.00 (17.31–87.87) | < 0.001 |
| - 2 (N = 64) | 3.3 (2.5–4.2) | > 100 (NA) | < 0.001 | > 100 (NA) | < 0.001 |
| First-line therapy | |||||
| - Only pembrolizumab (N = 124) | 9.7 (3.8–15.5) | 1.00 | - | 1.00 | - |
| - Pemetrexed-based (N = 75) | 13.3 (10.5–16.0) | 0.90 (0.63–1.27) | 0.559 | 0.83 (0.09–7.37) | 0.874 |
| - Paclitaxel-based (N = 17) | 13.3 (11.4–15.1) | 0.85 (0.42–1.71) | 0.854 | 1.58 (0.16–15.27) | 0.691 |
| Corticosteroidsa | |||||
| - No (N = 122) | 16.1 (12.4–20.3) | 1.00 | - | 1.00 | - |
| - Yes (N = 94) | 9.0 (6.5–11.5) | 1.76 (1.27–2.43) | 0.001 | 1.79 (1.20–2.66) | 0.004 |
| APAPb | |||||
| - No (N = 154) | 13.7 (11.2–16.3) | 1.00 | - | 1.00 | - |
| - Yes (N = 62) | 7.2 (4.2–10.2) | 1.41 (1.01–1.99) | 0.046 | 1.37 (0.93–2.04) | 0.108 |
| Systemic antibioticsc | |||||
| - No (N = 176) | 13.5 (11.2–15.7) | 1.00 | - | 1.00 | - |
| - Yes (N = 40) | 6.8 (4.7–8.8) | 1.63 (1.09–2.43) | 0.016 | 0.69 (0.40–1.18) | 0.184 |
| PPId | |||||
| - No (N = 158) | 13.4 (11.1–15.6) | 1.00 | - | 1.00 | - |
| - Yes (N = 58) | 10.8 (5.6–16.1) | 1.01 (0.71–1.43) | 0.951 | 1.09 (0.72–1.63) | 0.675 |
| Benzodiazepines (generic intake) | |||||
| - No (N = 108) | 11.7 (8.1–15.2) | 1.00 | - | 1.00 | - |
| - Yes (N = 108) | 13.7 (10.6–16.9) | 0.91 (0.66–1.25) | 0.566 | 0.69 (0.48–1.01) | 0.058 |
| Benzodiazepines (specific intake) | |||||
| - No (N = 108) | 11.7 (8.1–15.2) | 1.00 | - | 1.00 | - |
| - N-unsubstituted (N = 51) | 9.1 (6.0–12.2) | 1.57 (1.05–2.34) | 0.025 | 1.92 (1.20–3.06) | 0.006 |
| - N-substituted (N = 57) | 16.2 (10.4–21.9) | 0.64 (0.43–0.94) | 0.026 | 0.58 (0.38–0.88) | < 0.001 |
OS: overall 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