Crizotinib Outcomes in ALK-Positive NSCLC Patients with Brain Metastases Study

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. 2

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 3

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 Cohort for main study (n = 212) 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) See 2016 WCLC Abstract No. 929 Complete medical record through last crizotinib dose Cohort for present analyses (n = 33) 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 4

Results Patient Demographics & Clinical Characteristics Demographics Clinical Characteristics Age at crizotinib 57.6 (11.9) Deceased at date of chart 10 (30.2) initiation, mean (SD) review, n (%) Sex, n (%) Current/former smoker, n (%) 22 (66.7) Male 19 (57.6) ECOG at diagnosis, n (%) Female 14 (42.4) 0 or 1 18 (54.5) Ethnicity, n (%) 2 or 3 15 (45.5) White 25 (75.8) Adenocarcinoma histology, n 28 (84.8) Black 5 (15.2) (%) Asian/Pacific 3 (9.0) Crizotinib treatment duration 230 islander (days), median 5

Results Best Response (Primary Tumor) and Survival Patients Initiating Crizotinib as First-Line Tx (n = 22) Patients Initiating Crizotinib as Second/Later-Line Tx (n = 11) 4% Complete response Complete response 13% 20% 17% Partial response Partial response Stable disease Stable disease 18% 20% 60% Disease progression Disease progression 48% 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% 20% 40% 60% 80% 100% 6

Results Status of Brain Lesions During Crizotinib Treatment Intracranial Response During Crizotinib Treatment 100% 90% 27% Stable Disease 80% 44% 70% 14% Progressive Disease 60% 11% 50% Partial Intracranial Response 40% 41% 22% 30% Complete Intracranial Response 20% 22% 10% 18% 0% First-Line Initiators (n = 22) Second-Line Initiators (n = 11) Note: 71% of patients received either whole brain radiotherapy or stereotactic radiosurgery prior to crizotinib initiation. 7

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 8

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]. 9