Baseline clinical, pathological and treatment characteristics of patients with advanced LCNEC divided according to exposure to ICI
| Pts treated with ICI (group A, n=41) | Pts not treated with ICI (group B, n=84) | P value | All pts (n=125) | |
| Age, years—median (IQR) | 63 (58–68) | 67 (62–75) | 0.003 | 66 (61–73) |
| Sex, n (%) | 1.00 | |||
| Female | 16 (39) | 32 (38) | 48 (38) | |
| Male | 25 (61) | 52 (62) | 77 (62) | |
| Smoking history, n (%) | 1.00 | |||
| Current/past smoker | 36 (88) | 69 (82) | 105 (84) | |
| Never smoker | 5 (12) | 11 (13) | 16 (13) | |
| NA | 0 (0) | 4 (5) | 4 (3) | |
| Histological subtype, n (%) | 0.12 | |||
| LCNEC | 33 (80) | 73 (87) | 106 (85) | |
| Mixed LCNEC+SCLC | 6 (15) | 11 (13) | 17 (14) | |
| Mixed LCNEC+NSCLC | 2 (5) | 0 (0) | 2 (1) | |
| Stage, n (%)* | 0.77 | |||
| I/II | 4 (10) | 11 (13) | 15 (12) | |
| III/IV | 37 (90) | 71 (85) | 108 (87) | |
| NA | 0 (0) | 2 (2) | 2 (1) | |
| ECOG PS, n (%) | 0.02 | |||
| 0/1 | 31 (75) | 37 (44) | 68 (54) | |
| 2/3/4 | 6 (15) | 26 (31) | 32 (26) | |
| NA | 4 (10) | 21 (25) | 25 (20) | |
| Brain metastases, n (%) | 0.97 | |||
| Yes | 14 (34) | 26 (31) | 40 (32) | |
| No | 27 (66) | 46 (55) | 73 (58) | |
| NA | 0 (0) | 12 (14) | 12 (10) | |
| Liver metastases, n (%) | 0.80 | |||
| Yes | 15 (37) | 27 (32) | 42 (34) | |
| No | 26 (63) | 56 (67) | 82 (65) | |
| NA | 0 (0) | 1 (1) | 1 (1) | |
| Ki-67, %—median (IQR)† | 70 (60-80) | 70 (50-80) | 0.39 | 70 (50-80) |
| Molecular subtype | NA | |||
| SCLC-like | 6 (15) | 1 (1) | 7 (6) | |
| NSCLC-like | 10 (24) | 5 (6) | 15 (12) | |
| NA | 25 (61) | 78 (93) | 103 (82) | |
| PD-L1 TPS, n (%) | 0.15 | |||
| ≥50% | 3 (7) | 0 (0) | 3 (2) | |
| 1%–49% | 2 (5) | 4 (5) | 6 (5) | |
| <1% | 16 (39) | 10 (12) | 26 (21) | |
| NA | 20 (49) | 70 (83) | 90 (72) | |
| TMB, mut/Mb—median (IQR)‡ | 14 (10–17) | 21 (21) | 0.38 | 14 (10–21) |
| MSI-high, n (%)§ | 1 (2) | NA | NA | 1 (1) |
| Treatment details | ||||
| Chemotherapy, n (%) | 39 (95) | 62 (74) | 0.01 | 101 (81) |
| SCLC-based chemotherapy, n (%)¶ | 30 (73) | 51 (61) | 0.40 | 81 (65) |
| NSCLC-based chemotherapy, n (%)¶ | 15 (36) | 17 (20) | 0.11 | 32 (26) |
| Somatostatin analogs, n (%) | 0 (0) | 3 (3) | 0.55 | 3 (2) |
| Tyrosine kinase inhibitors, n (%) | 3 (7) | 2 (2) | 0.39 | 5 (4) |
| Systemic treatment lines, n (%) | <0.001 | |||
| 0 | 0 (0) | 21 (25) | 21 (17) | |
| 1 | 5 (12) | 47 (56) | 52 (42) | |
| 2 | 26 (64) | 11 (13) | 37 (30) | |
| 3 | 7 (17) | 4 (5) | 11 (9) | |
| 4 | 1 (2) | 1 (1) | 2 (1) | |
| 5 | 2 (5) | 0 (0) | 2 (1) | |
| ≥1 systemic treatment lines, n (%) | 41 (100) | 63 (75) | 0.001 | 104 (83) |
Statistically significant differences are indicated in bold.
*Stage at initial diagnosis.
†Assessed in 88 patients (group A, n=33; group B, n=55).
‡Assessed in eight pts (group A, n=7; group B, n=1).
§Assessed in eight pts (group A, n=8).
¶14 patients (n=6 and n=8%–15% and 10% of groups A and B, respectively) received both SCLC-based and NSCLC-based chemotherapy.
ECOG PS, Eastern Cooperative Oncology Group performance status score; ICI, immune check point inhibitors; LCNEC, large-cell neuroendocrine tumors of lung; MSI, microsatellite instability; mut/Mb, mutations per megabase; NA, not available/not applicable; NSCLC, non-small-cell lung cancer; PD-L1, programmed-death ligand 1; pts, patients; SCLC, small-cell lung cancer; TMB, tumor mutation burden; TPS, Tumor Proportion Score.