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Crizotinib outcomes in ALK- positive
advanced NSCLC patients with brain
metastases
Keith L. Davis, MA,1 James A. Kaye, MD, DrPH,2 Shrividya Iyer, PhD2
1RTI
Health Solutions, Research Triangle Park, NC/United States of
America, 2RTI Health Solutions, Waltham, MA/United States of
America, 3Pfizer, Inc. New York, NY/United States of America
Mini Oral Presentation at the 16th World Conference on Lung Cancer, Sep 6-9, 2015, Denver, CO, USA
Financial Disclosure: This study was sponsored by Pfizer, Inc.
Background
• Brain metastases are reported at initial diagnosis in 15-35% of
patients with ALK+ metastatic non-small cell lung cancer
(NSCLC)1-3
• Frequency of brain lesions can increase (up to 46% of ALK+
patients by one estimate4) over the course of first-line therapy
• Crizotinib is an oral tyrosine kinase inhibitor (TKI) with proven
efficacy against ALK+ tumors3,5
• Clinical benefits of crizotinib in ALK+ metastatic NSCLC patients
with brain metastases have been documented in trial data6 and in
single-case reports7
1. Doebele et al. Cancer 2012;118:4502-11. 2. Kang et al. Respir Med 2014;108:388-94. 3. Shaw et al. N Engl J Med 2013;368:2385-94.
4. Weickhardt et al. J Thorac Oncol 2012;7:1807-1814. 5. Ou et al. Ann Oncol 2014;25:415-22. 6. Costa DB et al. J Clin Oncol 2015. [Epub ahead of print].
7. Kinoshita Y et a.. BMJ Case Rep 2013. doi:10.1136/bcr-2013-200867.
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Rationale and Objectives
• The clinical experience of crizotinib-treated patients with
ALK+ metastatic NSCLC and brain metastases has not
been widely assessed in real-world settings
• To help fill this research gap, we assessed the following in a
small cohort of ALK+ metastatic NSCLC patients with brain
metastases:
– Demographic and clinical characteristics
– Objective response rate (ORR) of primary tumor during crizotinib
treatment and 1-year survival rates from crizotinib initiation
– Status of brain lesions (intracranial response [ICR]) during crizotinib
treatment
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Methods
• Retrospective chart review (anonymized data, IRB approved)
• Data abstraction performed in 2014 by pooled sample of 147
oncologists in the US (n = 107) and Canada (n = 40)
• Patient inclusion criteria:
– Adults (age ≥18) diagnosed with ALK+ metastatic NSCLC
– Received crizotinib as first- or later-line treatment
– First crizotinib treatment received between 8/1/2011
and 3/31/2013 (for US patients), or 4/12/2012 and
3/31/2013 (for Canadian patients)
Cohort for main
study (n = 212)
See 2016 WCLC
Abstract No. 929
– Complete medical record through last crizotinib dose
– Brain metastases present prior to or upon crizotinib initiation
Cohort for present
analyses (n = 33)
• Analyses were descriptive and exploratory
– Kaplan-Meier (K-M) methods used for 1-year survival rate estimates
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Results – Patient Demographics & Clinical Characteristics
Demographics
Age at crizotinib
57.6 (11.9)
Clinical Characteristics
Deceased at date of chart
initiation, mean (SD)
review, n (%)
Sex, n (%)
Current/former smoker, n (%)
Male
19 (57.6)
Female
14 (42.4)
5
22 (66.7)
ECOG at diagnosis, n (%)
Ethnicity, n (%)
0 or 1
18 (54.5)
2 or 3
15 (45.5)
White
25 (75.8)
Black
5 (15.2)
(%)
Asian/Pacific
3 (9.0)
Crizotinib treatment duration
islander
10 (30.2)
Adenocarcinoma histology, n
(days), median
28 (84.8)
230
Results – Best Response (Primary Tumor) and Survival
Patients Initiating Crizotinib as
First-Line Tx (n = 22)
4%
Patients Initiating Crizotinib as
Second/Later-Line Tx (n = 11)
Complete
response
13%
17%
18%
48%
Complete
response
20%
Partial
response
Partial
response
Stable
disease
Stable
disease
20%
60%
Disease
progression
Disease
progression
Not
assessed
Not
assessed
ORR = 60%
ORR = 61%
K-M Estimates of 1-Year Survival Probability from Crizotinib Initiation
Patients Initiating Crizotinib First-Line
80.7%
Patients Initiating Crizotinib Second/Later-Line
77.1%
0%
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20%
40%
60%
80%
100%
Results – Status of Brain Lesions During Crizotinib Treatment
Intracranial Response During Crizotinib Treatment
100%
90%
27%
80%
44%
Stable Disease
70%
14%
Progressive Disease
60%
11%
50%
40%
Partial Intracranial
Response
41%
22%
30%
Complete Intracranial
Response
20%
10%
18%
22%
First-Line Initiators (n = 22)
Second-Line Initiators (n = 11)
0%
• Note: 71% of patients received either whole brain radiotherapy or stereotactic radiosurgery
prior to crizotinib initiation.
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Study Limitations
• Estimates based on small subsample (n = 33) of a larger
multinational study
– Small sample size limited study to descriptive, exploratory analyses (no
multivariable adjustments for covariates)
– Results may not be generalizable to entire ALK+ metastatic NSCLC
population in the US or Canada
• No covariate adjustments
– ICR, for example, may be confounded by prior treatments (71% rec’d
either whole brain radiotherapy or stereotactic radiosurgery)
• Convenience sample
– Non-randomized population
– Timing and manner of assessments of ORR and ICR not protocol-driven
(i.e., not assessed at pre-defined intervals, but rather at time points
determined by the physicians in regular practice)
• Chart reviews subject to data entry/coding errors
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Conclusions
• Complete or partial response of the primary tumor during
crizotinib treatment was seen in a majority of patients (ORR
~60%)
• 1-year survival (~80%) was higher than a recent trial-based
report of ALK+ metastatic NSCLC patients with brain
metastases (~65%)6
• Results support emerging literature on the possible clinical
benefits of crizotinib in ALK+ metastatic NSCLC patients
with brain metastases
• Findings provide signal that outcomes may be further
optimized with earlier (first-line) initiation of crizotinib
6. Costa DB et al. J Clin Oncol 2015. [Epub ahead of print].
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