Table 1.
Patient characteristics and details of treatment.
| All Study Patients (N = 62) | TP53wtbas (n = 39) | TP53mutbas (n = 23) | ||
|---|---|---|---|---|
| TP53wtprogr (n = 30) | TP53mutconv (n = 9) | |||
| Age (median; IQR) | 51; 17 | 63; 20 | 65; 19 | |
| Sex (male/female) | 15/16 | 5/4 | 12/11 | |
| ECOG PS at diagnosis of stage IV (median; IQR) | 0; 0 | 0; 0 | 1; 0 | |
| Histology | adenocarcinoma 1 | 29/30 | 9/9 | 23/23 |
| ALK status | positive | all cases by inclusion criteria | ||
| EML4-ALK V3 2 | 8/24 | 5/9 | 8/20 | |
| Stage IV NSCLC | at initial diagnosis | 20/30 * | 9/9 | 21/23 |
| M1a | 7/20 | 1/9 | 5/21 | |
| by relapse of M0 NSCLC | 10/30 | 0/9 | 2/23 | |
| TP53 assessment at baseline + at progression 3 | ||||
| method | FFPE at BL +FFPE at PD 4 | 8/30 (neg + neg) | 2/9 (neg + pos) | See Table S1 |
| FFPE at BL +ctDNA at PD | 11/30 (neg + neg) | 7/9 (neg + pos) | ||
| FFPE at PD 4 | 6/30 (neg) | |||
| only ctDNA at PD | 5/30 (neg) | |||
| TKI line (start) at 2nd assessment (median; IQR) | 2; 1 | 2; 1 | ||
| treatment line at 2nd assessment (median; IQR) | 2; 3 | 4; 1 | ||
| - days after diagnosis of stage IV (median; IQR) | 702; 1056 | 752; 600 | ||
| ALK TKI treatment, next-line | ||||
| crizotinib | 14 | 2 | ||
| ceritinib | 7 | 4 | ||
| alectinib | 6 | 1 | ||
| brigatinib | 2 | - | ||
| - no. of patients 5 | 29/30 (97%) | 7/9 (78%) | ||
| - no. of patients with CBDP | 15/30 | 4/7 | ||
| ALK TKI treatment, all lines (1–8) | ||||
| crizotinib | 23 | 9 | 19 | |
| ceritinib | 12 | 9 | 5 | |
| alectinib | 14 | 4 | 10 | |
| brigatinib | 4 | 0 | 3 | |
| lorlatinib | 3 | 1 | 1 | |
| - no. of patients 5,6 | 29/30 (97%) | 9/9 (100%) | 22/23 (96%) | |
| Chemotherapy, all lines (1–8) | ||||
| platin-doublets | 15 | 8 | 7 | |
| monotherapy | 6 | 4 | 6 | |
| - no. of patients | 14/30 (47%) | 8/9 (89%) | 8/23 (35%) | |
| Summary of the complete treatment | ||||
| no. of treatment lines (mean; SD) | 3.0; 1.5 | 4.0; 1.7 | 2.4; 1.6 | |
| no. of TKI treatment lines (mean; SD) | 1.9; 1.2 | 2.6; 1.0 | 1.7; 1.1 | |
| patients with additional radiotherapy | 18/30 (60%) | 6/9 (67%) | 12/21 (57%) | |
| patients with additional surgical treatment 7 | 5/30 (17%) | 1/9 (11%) | 5/21 (24%) | |
| Follow-up in months (median (25th–75th percentile)) | 36 (28–94) | |||
TP53wtbas: TP53 wild-type at baseline; TP53wtprogr: TP53 wild-type at baseline and after disease progression; TP53mutconv: TP53 wild-type at baseline with detection of TP53 mutations at progression; TP53mutbas: TP53 mutated at baseline; IQR: interquartile range; neg: negative; SD: standard deviation; PS: performance status; BL: baseline; PD: disease progression; no.: number; CBDP: continuation of treatment beyond disease progression due to ongoing clinical benefit; * p < 0.05 compared to TP53mutconv and p < 0.05 compared to TP53mutbas. 1 1/30 TP53wtprogr patients had an EML4-ALK V2 (E20;A20)+ large-cell neuroendocrine lung carcinoma. 2 The ALK fusion could be typed in 53/62 cases. 3 For 3/30 TP53wtprogr cases, TP53 wild-type status at progression was evaluated by analysis of ctDNA samples obtained 24, 29 and 37 months later. 4 For 7/8 TP53wtprogr cases, also ctDNA at PD (neg); for 5/6 TP53wtprogr cases, also ctDNA at PD (neg). 5 One TP53wtprogr patient received definitive local treatment for oligometastatic disease and is still in remission without exposure to TKI; 2/9 TP53mutconv patients did not receive next-line treatment after reassessment of TP53 status due to rapid clinical deterioration (they had received TKI in previous lines). 6 One TP53mutbas patient has ongoing stable disease 18 months after first-line chemotherapy without initiation of next-line treatment. 7 Excluding video-assisted thoracoscopy and pleurodesis for pleural effusion.