Figures
- FIGURE 1
Patient disposition in the temporary authorisation for use (TAU) programme. ALK+: anaplastic lymphoma kinase positive; ROS1+: ROS proto-oncogene 1 positive; IMT: inflammatory fibroblastic tumour
Tables
- TABLE 1
Baseline characteristics of patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC)
Characteristic Patients (n=214) Age years (n=211) 58 (19–90) Sex (n=214) Female 111 (51.9) ECOG performance status (n=205) 0–1 145 (70.7) ≥2 60 (28.9) Histology (n=207) Adenocarcinoma 199 (96.1) Undifferentiated carcinoma 2 (1.0) Other 6 (2.9) Number of metastatic sites (n=177) 0–2 117 (66.1) ≥3 60 (33.9) Metastatic localizations (n=210) Brain 105 (50.0) ALK test method (n=203) FISH only 107 (52.7) IHC only 19 (9.4) FISH and IHC 74 (36.5) Other 3 (1.5) Time from initial diagnosis to inclusion in TAU months (n=206) 23.2 (1.7–192.8) Prior medication regimens (including crizotinib) (n=213) 1 (crizotinib only) 15 (7.0) 2 97 (45.5) >2 101 (47.4) Median 2 Treatment line for crizotinib administration# (n=213) 1 27 (12.7) 2 130 (61.0) 3 35 (16.4) >4 37 (17.4) Crizotinib as last prior regimen# (n=213) Yes 156 (73.2) Duration of crizotinib treatment months (n=208) 9.1 (0.1–52.0) 25%–75% 5.0–15.0 Reason to stop crizotinib# (n=222) Disease progression 203 (91.4) Toxicity 16 (7.2) Other 3 (1.4) Data are presented as n (%) or median (range) unless otherwise stated. ECOG: Eastern Cooperative Oncology Group; FISH: fluorescent in situ hybridisation; IHC: immunohistochemistry; TAU: temporary authorisation for use. #: crizotinib could be administered as more than one line/regimen for the same patient.
- TABLE 2
Physician-assessed response and treatment duration in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC)
Radiological tumour evaluation ALK+ NSCLC patients (n=149) CR 8 (5.4) PR 70 (47.0) SD 34 (22.8) PD 19 (12.8) Not realised 18 (12.1) ORR 78 (52.3) DCR 112 (75.2) Duration months (n=182) 3.9 (0.4–23.0) Data is presented as n (%) or median (range). CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; ORR: overall response rate; DCR: disease control rate.
- TABLE 3
Duration of ceritinib treatment according to duration of follow-up in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC)
All evaluable ALK+ patients# Patients with follow-up ≥6 months Patients with follow-up ≥12 months¶ Subjects n 182 136 71 Duration months 5.8 6.8 8.1 3.9 (0.4–23.0) 5.5 (0.4–23.0) 5.5 (0.4–23.0) Data are presented as mean or median (range) unless otherwise stated. #: discontinuation of ceritinib was documented for 117 out of 182 patients (64.2%) at the cut-off (64.3% maturity); ¶: 16 out of 71 patients (22.5%) were still receiving ceritinib or were censored at cut-off (77.5% maturity).
- TABLE 4
Physician-assessed response and treatment duration in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) according to subgroups based on Eastern Cooperative Oncology Group (ECOG) performance status and presence of brain metastases
Radiological tumour evaluation ECOG performance status Brain metastases 0–1 (n=134) 2–4 (n=51) Present (n=97) Absent (n=64) Assessed response Evaluable subjects 109 33 72 50 CR 8 (7.3) 0 (0.0) 2 (2.8) 4 (8.0) PR 52 (47.7) 14 (42.4) 33 (45.8) 26 (52.0) SD 28 (25.7) 4 (12.1) 18 (25.0) 6 (12.0) PD 11 (10.1) 8 (24.2) 8 (11.1) 8 (16.0) Not realised 9 (8.3) 6 (18.2) 10 (13.9) 5 (10.0) Not evaluable 1 (0.9) 1 (3.0) 1 (1.4) 1 (2.0) ORR 60 (55.0) 14 (42.4) 35 (48.6) 30 (60.0) Treatment duration Subjects 131 43 92 60 Duration months 4.6 (0.4–22.4) 2.3 (0.4–19.9) 3.3 (0.4–23.0) 4.5 (0.4–22.2) Data are presented as n, n (%) or median (range) unless otherwise stated. CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; ORR: overall response rate.
- TABLE 5
Physician-assessed response in patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) according to subgroups based on the number of previous lines of treatment, the duration of previous treatment with crizotinib and dose reduction
Radiological tumour evaluation Previous lines of treatment Duration of previous crizotinib treatment# Dose reduction¶ ≤2 lines (n=98) >2 lines (n=94) <Q1 (n=47) Q1−Q2 (n=47) Q2−Q3 (n=46) ≥Q3 (n=49) With dose reduction (n=84) Without dose reduction (n=109) Assessed response Evaluable subjects 72 76 36 31 35 43 74 75 CR 5 (6.9) 3 (3.9) 0 (0.0) 4 (12.9) 2 (5.7) 2 (4.7) 5 (6.8) 3 (4.0) PR 35 (48.6) 35 (46.1) 13 (36.1) 12 (38.7) 20 (57.1) 23 (53.5) 36 (48.6) 34 (45.3) SD 18 (25.0) 15 (19.7) 10 (27.8) 5 (16.1) 7 (20.0) 10 (23.3) 17 (23.0) 17 (22.7) PD 10 (13.9) 9 (11.8) 10 (27.8) 3 (9.7) 3 (8.6) 3 (7.0) 8 (10.8) 11 (14.7) Not realised 3 (4.2) 13 (17.1) 3 (8.3) 5 (16.1) 3 (8.6) 5 (11.6) 6 (8.1) 10 (13.3) Not evaluable 1 (1.4) 1 (1.3) 0 (0.0) 2 (6.5) 0 (0.0) 0 (0.0) 2 (2.7) 0 (0.0) ORR 40 (55.5) 38 (50.0) 13 (36.1) 16 (51.6) 22 (62.8) 25 (58.2) 41 (55.4) 37 (49.3) Treatment duration Subjects 91 90 43 45 43 47 83 99 Duration months 3.8 (0.4–23.0) 3.7 (0.4–22.4) 2.3 (0.4–15.9) 3.0 (0.4–23.0) 5.1 (0.4–19.9) 7.6 (0.9–22.2) 4.9 (0.4–22.2) 2.7 (0.4–23.0) Data are presented as n, n (%) or median (range). CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; ORR: overall response rate. #: <Q1 means <5 months of crizotinib, Q1–Q2 means 5 to <9.2 months of crizotinib, Q2–Q3 means 9.2 to <16 months of crizotinib >Q3 means >16 months of crizotinib. ¶: dose reduction is <750 mg·day−1 of ceritinib or a temporary discontinuation in the first 6 months of treatment.
- TABLE 6
Summary of adverse events (AEs) suspected of being related to the study drug
Event Any grade (n=208) Severe (n=208) Any AE 138 (66.3) 105 (50.3) Any AE considered to be drug related 118 (56.7) 74 (35.6) Drug reduction and/or interruption 67 (32.2) Drug discontinuation 13 (6.3) Most common AEs Diarrhoea 46 (22.1) 12 (5.8) Nausea 35 (16.8) 11 (5.3) Vomiting 34 (16.3) 11 (5.3) Hepatic toxicity (ALT/AST-increased or other) 41 (19.7) 26 (12.5) Abdominal pain 12 (5.8) 1 (0.5) Weight decrease 12 (5.8) 5 (2.4) Asthenia 10 (4.8) 7 (3.4) Decreased appetite 9 (4.3) 5 (2.4) Creatinine increase/renal insufficiency 14 (6.7) 8 (3.8) Fatigue 6 (2.9) 2 (1.0) Pericardial tamponade/effusion 5 (2.4) 3 (1.4) Hyperglycaemia 3 (1.4) 2 (1.0) Dyspnoea 3 (1.4) 3 (1.4) Thrombocytopenia 4 (1.9) 3 (1.4) Skin disorders 2 (1.0) 0 (0.0) Dehydration 2 (1.0) 2 (1.0) Data are presented as n (%). ALT: alanine aminotransferase; AST: aspartate aminotransferase.
- TABLE 7
Characteristics and outcomes of patients from the French temporary authorisation for use (TAU) ceritinib study with other ceritinib data in crizotinib-pretreated patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC)
French TAU ceritinib study ASCEND-1 (phase 1) Gainor cohort ASCEND-2 (phase 2) ASCEND-5 (phase 3) Subjects n 214 163 73# 140 115 ECOG % PS 0–1 70.8 87.1 NA 85.7 92.2 PS 2–4 29.3 12.9 NA 14.3¶ 7.8¶ Prior lines % 1 7 16 NA 0 0 2 45.5 27.6 NA 43.6 87.8 >2 47.4 56.0 NA 56.4 11.3+ Brain metastases % 51 61 NA 71 56.5 ORR % 52.4 56.4 NA 38.6 39.1 DCR % 75.2 74.2 NA 77.1 76.5 Median ceritinib duration/exposure months 3.9 (all patients)
5.5 (>12 months follow-up, 78% maturity)Median PFS months NA 6.9 7.8 5.7 5.4 Median OS months Not evaluable or not mature 16.7 49.4 (from diagnosis)
30.3 (from crizotinib start)14.9 (42% maturity) 18.1 (∼50% maturity) Dose reduction/interruption % 32.2 62 (reduction)
74 (interruption)NA 54.3 80.0 Discontinuation due to AEs % 6.3 11 NA 7.9 5.2 ECOG: Eastern Cooperative Oncology Group; PS: performance status; NA: not available; ORR: objective response rate; DCR: disease control rate; PFS: progression-free survival; OS: overall survival; AE: adverse event. #: 71 subjects from ASCEND-1; ¶: PS 2; +: three prior lines of therapy.
Supplementary Material
C. Audigier-Valette 00058-2017_Audigier-Valette
F. Barlesi 00058-2017_Barlesi
B. Besse 00058-2017_Besse
A. Buturuga 00058-2017_Buturuga
J. Cadranel 00058-2017_Cadranel
A.B. Cortot 00058-2017_Cortot
E. Dansin 00058-2017_Dansin
S. Friard 00058-2017_Friard
H. Lena 00058-2017_Lena
B. Mennecier 00058-2017_Mennecier
D. Moro-Sibilot 00058-2017_Moro-Sibilot
M. Perol 00058-2017_Perol
K. Slimane 00058-2017_Slimane
L. Thiberville 00058-2017_Thiberville
A. Vergnenegre 00058-2017_Vergnenegre
V. Westeel 00058-2017_Westeel
