Patient characteristics
| Variable | Unadjusted population | PSM-adjusted population | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| All patients (N = 258) | No-BZD cohort (N = 150) | BZD cohort (N = 108) | P value | SMD | All patients (N = 216) | No-BZD cohort(N = 108) | BZD cohort (N = 108) | P value | SMD | |
| Age | ||||||||||
| - Mean (SD), years | 70.0 (8.4) | 70.0 (7.9) | 69.5 (9.0) | 0.332 | - | 70.0 (8.43) | 70.0 (7.77) | 69.5 (9.04) | 0.457 | - |
| - ≥ 70 years | 136 (52.7%) | 82 (54.7%) | 54 (50.0%) | 0.459 | 0.046 | 111 (51.4%) | 57 (52.8%) | 54 (50.0%) | 0.685 | 0.027 |
| Sex | ||||||||||
| - Female | 78 (30.2%) | 40 (26.7%) | 38 (35.2%) | 0.207 | 0.093 | 74 (34.3%) | 36 (33.3%) | 38 (35.2%) | 0.776 | 0.018 |
| - Male | 180 (69.8%) | 110 (73.3%) | 70 (64.8%) | 142 (65.7%) | 72 (66.7%) | 70 (64.8%) | ||||
| ECOG PS | ||||||||||
| - 0 or 1 | 208 (80.6%) | 120 (80.0%) | 88 (81.5%) | 0.766 | 0.014 | 175 (81.0%) | 87 (80.6%) | 88 (81.5%) | 0.863 | 0.009 |
| - 2 | 50 (19.4%) | 30 (20.0%) | 20 (18.5%) | 41 (19.0%) | 21 (19.4%) | 20 (18.5%) | ||||
| Histologic subtype | ||||||||||
| - Nonsquamous | 202 (78.3%) | 118 (78.7%) | 84 (77.8%) | 0.864 | < 0.001 | 167 (77.3%) | 83 (76.9%) | 84 (77.8%) | 0.872 | 0.009 |
| - Squamous | 56 (21.7%) | 32 (21.3%) | 24 (22.2%) | 49 (22.7%) | 25 (23.1%) | 24 (22.2%) | ||||
| No. of metastatic sites | ||||||||||
| - ≤ 2 | 138 (53.5%) | 79 (52.7%) | 59 (54.6%) | 0.755 | 0.019 | 120 (55.6%) | 61 (56.5%) | 59 (54.6%) | 0.785 | 0.067 |
| - > 2 | 120 (46.5%) | 71 (47.3%) | 49 (45.4%) | 96 (44.4%) | 47 (43.5%) | 49 (45.4%) | ||||
| Bone metastasis | 53 (20.5%) | 30 (19.1%) | 23 (21.3%) | 0.799 | < 0.001 | 44 (20.4%) | 21 (19.4%) | 23 (21.3%) | 0.737 | 0.055 |
| Brain metastasis | 58 (22.5%) | 30 (20.0%) | 28 (25.9%) | 0.261 | < 0.001 | 55 (25.5%) | 27 (25.0%) | 28 (25.9%) | 0.877 | 0.059 |
| Liver metastasis | 28 (10.9%) | 19 (12.7%) | 9 (8.3%) | 0.270 | 0.043 | 20 (9.3%) | 11 (10.2%) | 9 (8.3%) | 0.641 | 0.039 |
| PD-L1 TPS | ||||||||||
| - < 1% | 80 (31.0%) | 45 (30.0%) | 35 (32.4%) | 0.066 | 0.326 | 71 (32.9%) | 36 (33.3%) | 35 (32.4%) | 0.663 | 0.083 |
| - ≥ 1% and ≤ 49% | 22 (8.5%) | 8 (5.3%) | 14 (13.0%) | 22 (10.2%) | 8 (7.4%) | 14 (13.0%) | ||||
| - ≥ 50% | 156 (60.5%) | 97 (64.7%) | 59 (54.6%) | 123 (56.9%) | 64 (59.3%) | 59 (54.6%) | ||||
| BMI | ||||||||||
| - Mean (SD), kg/m2 | 25.1 (4.80) | 24.8 (5.0) | 25.6 (4.5) | 0.635 | < 0.001 | 25.9 (4.87) | 26.0 (5.15) | 25.6 (4.55) | 0.233 | - |
| - ≥ 25 | 130 (50.4%) | 73 (48.7%) | 57 (52.8%) | 0.515 | 114 (52.8%) | 57 (52.8%) | 57 (52.8%) | 0.999 | < 0.001 | |
| Smoking habits | ||||||||||
| - Never | 23 (8.9%) | 14 (9.3%) | 9 (8.3%) | 0.781 | < 0.001 | 20 (9.3%) | 11 (10.2%) | 9 (8.3%) | 0.641 | < 0.001 |
| - Ever | 235 (91.1%) | 136 (90.7%) | 99 (91.7%) | 196 (90.7%) | 97 (89.8%) | 99 (91.7%) | ||||
| Previous thoracic RT | 35 (13.6%) | 16 (10.7%) | 19 (17.6%) | 0.109 | < 0.001 | 28 (13.0%) | 9 (8.3%) | 19 (17.6%) | 0.043 | < 0.001 |
| LIPI score | ||||||||||
| - 0 | 100 (38.8%) | 60 (40.0%) | 40 (37.0%) | 0.740 | < 0.001 | 84 (38.9%) | 44 (40.7%) | 40 (37.0%) | 0.742 | < 0.001 |
| - 1 | 88 (34.1%) | 52 (34.7%) | 36 (33.3%) | 68 (31.5%) | 32 (29.6%) | 36 (33.3%) | ||||
| - 2 | 70 (27.1%) | 38 (25.3%) | 32 (29.7%) | 64 (29.6%) | 32 (29.6%) | 32 (29.6%) | ||||
| First-line therapy | ||||||||||
| - Only pembrolizumab | 156 (60.5%) | 96 (64.0%) | 60 (55.6%) | 0.377 | < 0.001 | 124 (57.4%) | 64 (59.3%) | 60 (55.6%) | 0.596 | < 0.001 |
| - Pemetrexed-based | 84 (32.6%) | 45 (30.0%) | 39 (36.1%) | 75 (34.7%) | 36 (33.3%) | 39 (36.1%) | ||||
| - Paclitaxel-based | 18 (7.0%) | 9 (6.0%) | 9 (8.3%) | 17 (7.9%) | 8 (7.4%) | 9 (8.3%) | ||||
| Corticosteroidsa | 103 (39.9%) | 54 (36.0%) | 49 (45.4%) | 0.129 | < 0.001 | 94 (43.5%) | 45 (41.7%) | 49 (45.4%) | 0.585 | < 0.001 |
| APAPb | 101 (39.1%) | 67 (44.7%) | 34 (31.5%) | 0.032 | 0.131 | 62 (28.7%) | 28 (25.9%) | 34 (31.5%) | 0.369 | < 0.001 |
| Systemic antibioticsc | 58 (22.5%) | 38 (25.3%) | 20 (18.5%) | 0.196 | 0.068 | 40 (18.5%) | 20 (18.5%) | 20 (18.5%) | 0.999 | < 0.001 |
| PPId | 88 (34.1%) | 59 (39.3%) | 29 (26.9%) | 0.036 | 0.124 | 58 (26.9%) | 29 (26.9%) | 29 (26.9%) | 0.999 | < 0.001 |
| Specific BZD intake | ||||||||||
| - N-substitutede | 57 (22.1%) | - | 57 (52.8%) | - | - | 57 (26.4%) | - | 57 (52.8%) | - | - |
| - N-unsubstitutedf | 51 (19.7%) | 51 (47.2%) | 51 (23.6%) | 51 (47.2%) | ||||||
PSM: propensity score matching; BZD: benzodiazepine; SMD: standardized mean difference; SD: standard deviation; 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; e N-substituted denoted intake of alprazolam, diazepam, bromazepam, or triazolam; f N-unsubstituted denoted intake of lorazepam, clonazepam, delorazepam, or lormetazepam