Crizotinib outcomes in ALK- positive advanced NSCLC patients with brain metastases

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

Keith L. Davis, MA,1 James A. Kaye, MD, DrPH,2 Shrividya Iyer, PhD2

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.

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• 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.

Background

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• 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

Rationale and Objectives

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• 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)

– Complete medical record through last crizotinib dose

– Brain metastases present prior to or upon crizotinib initiation

• Analyses were descriptive and exploratory– Kaplan-Meier (K-M) methods used for 1-year survival rate estimates

Methods

Cohort for main study (n = 212)

See 2016 WCLC Abstract No. 929

Cohort for present analyses (n = 33)

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Results – Patient Demographics & Clinical Characteristics

Demographics

Age at crizotinib

initiation, mean (SD)

57.6 (11.9)

Sex, n (%)

Male 19 (57.6)

Female 14 (42.4)

Ethnicity, n (%)

White 25 (75.8)

Black 5 (15.2)

Asian/Pacific

islander

3 (9.0)

Clinical Characteristics

Deceased at date of chart

review, n (%)

10 (30.2)

Current/former smoker, n (%) 22 (66.7)

ECOG at diagnosis, n (%)

0 or 1 18 (54.5)

2 or 3 15 (45.5)

Adenocarcinoma histology, n

(%)

28 (84.8)

Crizotinib treatment duration

(days), median

230

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Results – Best Response (Primary Tumor) and Survival

13%

48%

17%

17%

4%

Patients Initiating Crizotinib as First-Line Tx (n = 22)

Complete response

Partial response

Stable disease

Disease progression

Not assessed

ORR = 61%

60%20%

20%

Patients Initiating Crizotinib as Second/Later-Line Tx (n = 11)

Complete response

Partial response

Stable disease

Disease progression

Not assessedORR = 60%

Patients Initiating Crizotinib Second/Later-Line

Patients Initiating Crizotinib First-Line

0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

77.1%

80.7%

K-M Estimates of 1-Year Survival Probability from Crizotinib Initiation

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First-Line Initiators (n = 22) Second-Line Initiators (n = 11)0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

18% 22%

41%22%

14%

11%

27%

44%

Intracranial Response During Crizotinib Treatment

Stable Disease

Progressive Disease

Partial Intracranial Response

Complete Intracranial Response

Results – Status of Brain Lesions During Crizotinib Treatment

• Note: 71% of patients received either whole brain radiotherapy or stereotactic radiosurgery prior to crizotinib initiation.

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• 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

Study Limitations

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• 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

Conclusions

6. Costa DB et al. J Clin Oncol 2015. [Epub ahead of print].