NSCLC: ALEX trial

Abbreviations

No EU-CTR

  • ALEX references
    2017-08-31
    Solange Peters
    Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer
Investigated (inv)
Comparator (comp)

ALEC

CRIZ

152

151

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

ALK poz.

Stage:

meta

Line of therapy:

L1

Primary
ALEC
CRIZ
HR
p
PFS @1yr
68.4%
48.7%
0.47 (0.34-0.65)
<0.001
Secondaries
ALEC
CRIZ
HR
p
CNS progression @1yr
12%
45%
0.16 (0.10-0.28)
<0.001
ORR
82.9%
75.5%
na
0.09
OS
Cumulative Incidence of CNS Progression @1yr
9.4%
41.4%
(all grades, %)
ALEC
CRIZ
p
Any AE grade ≥3
41%
50%
NA
Serious AE (gr.3-5)
28%
29%
NA
AE leading to dose interruption
19%
25%
NA
Nausea
14%
48%
NA
Diarrhea
12%
45%
NA
Vomiting
7%
38%
NA
ALT increased
15%
30%
NA
AST increased
14%
25%
NA
Blood bilirubin increased
15%
1%
NA
γ-Glutamyltransferase increased
1%
7%
NA
Peripheral edema
17%
28%
NA
Dizziness
8%
14%
NA
Dysgeusia
3%
19%
NA
Anemia
20%
5%
  • Inclusion
  • Exclusion

- Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test - Life expectancy of at least 12 weeks - Eastern cooperative oncology group performance status (ECOG PS) of 0-2 - Participants with no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC - Adequate renal, and hematologic function - Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment - Measurable disease by response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) prior to the administration of study treatment - Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline) - Negative pregnancy test for all females of child bearing potential - Use of highly effective contraception as defined by the study protocol

- Participants with a previous malignancy within the past 3 years - Any gastrointestinal (GI) disorder or liver disease - National cancer institute common terminology criteria for adverse events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia) - History of organ transplant - Co-administration of anti-cancer therapies other than those administered in this study - Participants with baseline QTc greater than (>) 470 milliseconds or symptomatic bradycardia - Recipient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment - Recipient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose for all participants and while on treatment through the end of the study for crizotinib-treated participants only - History of hypersensitivity to any of the additives in the alectinib and crizotinib drug formulation - Pregnancy or lactation - Any clinically significant disease or condition (or history of) that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in this study - Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry

Characteristics
ALEC
CRIZ
Agedc-comma sex
Median (range) yr
58 (25–88)
54 (18–91)
Male - no.(%)
68 (45)
64 (42)
Female - no.(%)
84 (55)
87 (58)
Race - no.(%)
Asian
69 (45)
69 (46)
Non-Asian
83 (55)
82 (54)
ECOG performance status - no.(%)
0 or 1
142 (93)
141 (93)
2
10 (7)
10 (7)
Smoking status - no.(%)
Active smoker
12 (8)
5 (3)
Former smoker
48 (32)
48 (32)
Nonsmoker
92 (61)
98 (65)
Current stage of disease - no.(%)
IIIB
4 (3)
6 (4)
IV
148 (97)
145 (96)
Histologic type - no.(%)
Adenocarcinoma
137 (90)
142 (94)
Large-cell carcinoma
0
3 (2)
Mixed with predominantly adenocarcinoma component
0
1 (1)
Squamous-cell carcinoma
5 (3
2 (1)
Histologic type - no.(%)
Undifferentiated
4 (3)
0
Other
6 (4)
3 (2)
CNS metastases - no.(%)
Yes
64 (42)
58 (38)
No
88 (58)
93 (62)
Treatment for CNS metastases - no./total no.(%)
Brain surgery
1/27 (4)
1/22 (5)
Radiosurgery
5/27 (19)
4/22 (18)
Whole-brain radiotherapy
17/27 (63)
16/22 (73)
Other
4/27 (15)
1/22 (5)
Previous brain radiation - no.(%)
Yes
26 (17)
21 (14)
No
126 (83)
130 (86)
Ad-hoc:
no.pts inv.
no.pts comp.
ALEC
CRIZ
HR
p
  • PFS @1yr
analisys of PFS @1yr
ALEC
CRIZ
HR (95% CI)
Age (n)
<65 yr (233)
0.48 (0.34–0.70)
≥65 yr (70)
0.45 (0.24–0.87)
Sex (n)
Male (132)
0.61 (0.38–0.98)
Female (171)
0.39 (0.25–0.60)
Race (n)
Asian (38)
0.46 (0.28–0.75)
Non-Asian (165)
0.49 (0.32–0.75)
Smoking status (n)
Nonsmoker (190)
0.44 (0.29–0.66)
Former smoker (96)
0.42 (0.23–0.77)
ECOG performance status (n)
0 (97)
0.40 (0.21–0.77)
1 (186)
0.48 (0.32–0.71)
CNS metastases at baseline (n)
Yes (122)
0.40 (0.25–0.64)
No (181)
0.51 (0.33–0.80)
Previous brain radiation (n)
Yes (47)
0.33 (0.14–0.74)
No (256)
0.52 (0.36–0.73)
analisys of
ALEC
CRIZ
HR (95% CI)