Patient characteristics in the discovery cohort
| All patients (N=75) | Low PERLS (N=67) | High PERLS (N=8) | P value | ||
| Age in years, median (IQR) | 61 (55.5; 70.5) | 61 (56; 71.5) | 55.5 (52.75; 61.5) | 0.974 | |
| Sex, n (%) | Female | 35 (46.7) | 32 (47.8) | 3 (37.5) | 0.716 |
| Male | 40 (53.3) | 35 (52.2) | 5 (62.5) | ||
| Smoking history, n (%) | Never | 8 (10.8) | 6 (9.1) | 2 (25) | 0.396 |
| Former | 39 (52.7) | 35 (53.0) | 4 (50) | ||
| Active | 27 (36.5) | 25 (37.9) | 2 (25) | ||
| Missing | * | * | 0 | ||
| Histology, n (%) | Adenocarcinoma | 61 (81.3) | 53 (79.1) | 8 (100) | 0.535 |
| Squamous | 11 (14.7) | 11 (16.4) | 0 (0) | ||
| Other* | 3 (4) | 3 (4.5) | 0 (0) | ||
| TNM†, n (%) | III | 13 (17.3) | 12 (17.9) | 1 (12.5) | * |
| IV | 62 (82.7) | 55 (82.1) | 7 (87.5) | ||
| Tumorous PD-L1 (% tumorous cells), n (%) | <1 | 10 (25) | 8 (22.9) | 2 (40) | 0.654 |
| 1%–49 | 6 (15) | 6 (17.1) | 0 (0) | ||
| >49 | 24 (60) | 21 (60) | 3 (60) | ||
| Missing | 35 | 32 | ‡ | ||
| Main molecular alteration, n (%) | K-RAS | 16 (37.2) | 16 (37.2) | 0 (0) | * |
| Wild-type‡ | 18 (41.9) | 18 (41.9) | 0 (0) | ||
| Targetable§ | 9 (20.9) | 9 (20.9) | 0 (0) | ||
| Missing | 32 | 24 | 8 | ||
| N metastatic sites, n (%) | ≤2 | 54 (72) | 49 (73.1) | 5 (62.5) | 0.679 |
| >2 | 21 (28) | 18 (26.9) | 3 (37.5) | ||
| ECOG PS, n (%) | 0–1 | 65 (86.7) | 57 (85.1) | 8 (100) | 0.587 |
| † | 10 (13.3) | 10 (14.9) | 0 (0) | ||
| Lines of prior therapy, n (%) | 0 | 6 (8) | 4 (6.0) | 2 (25) | 0.121 |
| ≥1 | 69 (92) | 63 (94.0) | 6 (75) | ||
| Prior chemotherapy, n (%) | No | 6 (8) | 4 (6.0) | 2 (25) | 0.121 |
| Yes | 69 (92) | 63 (94.0) | 6 (75) | ||
| Prior radiotherapy, n (%) | No | 51 (68) | 45 (67.2) | 6 (75) | * |
| Yes | 24 (32) | 22 (32.8) | 2 (25) | ||
| dNLR ≥3, n (%) | No | 36 (60) | 30 (57.7) | 6 (75) | 0.457 |
| Yes | 24 (40) | 22 (42.3) | 2 (25) | ||
| Missing | 15 | 15 | 0 | ||
| IrAEs (grade ≥3 or requiring CS)¶ | Yes | 5 (67) | 4 (6) | 1 (13) | 0.437 |
| No | 70 (33) | 63 (94) | 7 (87) | ||
| LDH≥ULN, n (%) | No | 20 (47.6) | 17 (46.0) | 3 (60) | 0.656 |
| Yes | 22 (52.4) | 20 (54.1) | 2 (40) | ||
| Missing | 33 | 30 | ‡ | ||
| LIPI score**, n (%) | Good | 10 (24.4) | 8 (22.2) | 2 (40) | 0.482 |
| Intermediate | 22 (53.7) | 19 (52.8) | 3 (60) | ||
| Poor | 9 (22.0) | 9 (25) | 0 (0) | ||
| NA | 34 | 31 | ‡ |
*Large cell lung cancer, non-small cell lung cancer, not otherwise specified.
†TNM stage eighth edition.
‡Absence of EGFR mutations, KRAS, ALK, ROS1 rearrangements.
§EGFR mutations, ALK, ROS1 rearrangement, HER2 mutations, MET alterations, BRAF mutations. Radiotherapy (including stereotactic radiotherapy) on any site (including bone or central nervous system).
¶Two patients with grade 3 colitis, one with grade 3 pneumonitis and two patients with grade 2 pneumonitis requiring cortico-steroids treatment.
**LIPI high: dNLR ≥3 and LDH ≥ULN; LIPI intermediate: dNLR <3 and LDH ≥ULN or dNLR ≥3 and LDH <ULN; LIPI low: dNLR <3 and LDH <ULN.
dNLR, derived neutrophil to lymphocyte ratio (neutrophils/(leukocytes -neutrophils)); IrAEs, immune related adverse events; LDH, lactate dehydrogenase; LIPI, lung immune prognostic index; PD-L1, programmed cell death-ligand 1 ; PS, performance status; TNM, tumour, node, metastases; ULN, upper limit of normal.