NSCLC: CROWN trial

Abbreviations

No EU-CTR

  • CROWN references
    2020-11-19
    Alice T. Shaw
    First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer
Investigated (inv)
Comparator (comp)

LORL

CRIZ

149

147

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

ALK poz.

Stage:

meta

Line of therapy:

L1

Primary
LORL
CRIZ
HR
p
PFS @1yr
78%
39%
0.28 (0.19-0.41)
<0.001
Secondaries
LORL
CRIZ
HR
p
ORR
76%
58%
na
na
ORR measurable brain meta
82%
23%
na
na
Cumulative Incidence of CNS Progr as First Event
2.8%
33.2%
0.06 (0.02–0.18)
(all grades, %)
LORL
CRIZ
p
Any AE grade ≥3
72%
56%
NA
Treatment discontinuation
7%
9%
NA
Hypercholesterolemia
70%
4%
NA
Hypertriglyceridemia
64%
6%
NA
Edema
55%
39%
NA
Peripheral neuropathy
34%
15%
NA
Cognitive effects
21%
6%
NA
Diarrhea
21%
52%
NA
Anemia
19%
8%
NA
Hypertension
18%
2%
NA
Vision disorder
18%
39%
NA
Increased ALT level
17%
34%
NA
Constipation
17%
30%
NA
Hyperlipidemia
11%
0%
  • Inclusion
  • Exclusion

- Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously irradiated. CNS metastases allowed if asymptomatic and not currently requiring corticosteroid treatment. - Availability of an archival FFPE tissue specimen. - No prior systemic NSCLC treatment. - ECOG PS 0, 1, or 2. - Age ≥18 years . - Adequate Bone Marrow, Liver, Renal, Pancreatic Function - Negative pregnancy test for females of childbearing potential

- Spinal cord compression unless good pain control attained - Major surgery within 4 weeks prior to randomization. - Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Whole brain irradiation within 4 weeks prior to randomization - Active bacterial, fungal, or viral infection - Clinically significant cardiovascular disease, active or within 3 months prior to enrollment. Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation, bradycardia or congenital long QT syndrome - Predisposing characteristics for acute pancreatitis in the last month prior to randomization. - History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease - Active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, LCIS/DCIS of the breast, or localized prostate cancer) within the last 3 years prior to randomization. - Concurrent use of any of the following food or drugs within 12 days prior to the first dose of lorlatinib or crizotinib. • known strong CYP3A inhibitors . • known strong CYP3A inducers • known P gp substrates with a narrow therapeutic index - Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days prior to the first dose of lorlatinib or crizotinib. - Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results - Investigational site staff members directly involved in the conduct of the study and their family members, or Pfizer employees, including their family members, directly involved in the conduct of the study. - Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

Characteristics
LORL
CRIZ
Agedc-comma sex
Median age (range) yr
61 (51-69)
56 (45-66)
Male - no(%)
65 (44)
56 (38)
Female - no(%)
84 (56)
91 (62)
Race or ethnic group - no(%)
White
72 (48)
72 (49)
Asian
65 (44)
65 (44)
Black
0
1 (1)
Missing
12 (8)
9 (6)
ECOG performance-status score - no(%)
0
67 (45)
57 (39)
1
79 (53)
81 (55)
2
3 (2)
9 (6)
Smoking status - no(%)
Never smoked
81 (54)
94 (64)
Previous smoker
55 (37)
43 (29)
Current smoker
13 (9)
9 (6)
Current stage of disease - no(%)
IIIA
1 (1)
0
IIIB
12 (8)
8 (5)
IV
135 (91)
139 (95)
Other
1 (1)
0
Histologic type - no(%)
Adenocarcinoma
140 (94)
140 (95)
Adenosquamous carcinoma
6 (4)
5 (3)
Large-cell carcinoma
0
1 (1)
Squamous-cell carcinoma
3 (2)
1 (1)
Other
Use of previous anticancer drug therapy - no(%)
12 (8)
9 (6)
Previous brain radiotherapy - no(%)
9 (6)
10 (7)
Brain metastases at baseline - no(%)
38 (26)
40 (27)
Ad-hoc:
no.pts inv.
no.pts comp.
LORL
CRIZ
HR
p
  • PFS @1yr
analisys of PFS @1yr
LORL
CRIZ
HR (95% CI)
Age
<65 yr
0.22 (0.13-0.37)
≥65 yr
0.35 (0.20-0.64)
Sex
Male
0.31 (0.18-0.54)
Female
0.26 (0.16-0.44)
Ethnic origin
Asian
0.47 (0.27-0.82)
Non-Asian
0.19 (0.11-0.32)
ECOG PS
0/1
0.28 (0.19-0.42)
Smoking status
Never
0.24 (0.14-0.40)
Current/Former
0.36 (0.20-0.63)
Presence of brain metastases
Yes
0.20 (0.10-0.43)
No
0.32 (0.20-0.49)
Histology
Adenocarcinoma
0.26 (0.18-0.39)
analisys of
LORL
CRIZ
HR (95% CI)