XALKORI was first approved in 2011 through the accelerated approval program of the U.S. Food and Drug Administration (FDA). It was granted regular approval in 2013 in the U.S. based on the results of PROFILE 1007, a Phase 3 study demonstrating that XALKORI significantly prolonged PFS in previously treated patients with ALK-positive advanced NSCLC when compared to single agent chemotherapy. To date, more than 8,000 patients have been treated with XALKORI 1, now approved in 74 countries 2, including Australia, Canada, China, Japan, South Korea and the European Union.About Non-Small Cell Lung Cancer Lung cancer is the leading cause of cancer death worldwide. 3 NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting. 4 Approximately 75 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease where the five-year survival rate is only 5 percent. 5,6,7 XALKORI ® (crizotinib) Indication and Important Safety Information XALKORI is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. Hepatotoxicity: Drug-induced hepatotoxicity with fatal outcome occurred in 0.2% of patients treated with XALKORI across clinical trials (n=1225). Transaminase elevations generally occurred within the first 2 months of treatment. Monitor with liver function tests including ALT and total bilirubin every 2 weeks during the first 2 months of treatment, then once a month and as clinically indicated. Permanently discontinue for ALT or AST elevation greater than 3 times ULN with concurrent total bilirubin elevation greater than 1.5 times ULN (in the absence of cholestasis or hemolysis), otherwise temporarily suspend and dose reduce XALKORI as indicated. Pneumonitis: Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with XALKORI. Across clinical trials (n=1225), 2.5% of XALKORI-treated patients had any grade ILD, 0.9% of patients had Grade 3 or 4, and 0.5% had fatal cases. These cases generally occurred within 2 months after the initiation of treatment. Monitor patients for pulmonary symptoms indicative of pneumonitis. Exclude other causes and permanently discontinue XALKORI in patients with drugrelated pneumonitis. QT Interval Prolongation: QTc prolongation can occur in patients treated with XALKORI. Across clinical trials (n=1225), QTc prolongation (all grades) was observed in 2.7% of patients and QTc greater than 500 ms on at least 2 separate ECGs occurred in 1.4% of patients. Avoid use of XALKORI in patients with congenital long QT syndrome. Consider periodic monitoring with electrocardiograms and electrolytes in patients who have a history of or predisposition for QTc prolongation, or who are taking medications that prolong the QT interval. Permanently discontinue XALKORI in patients who develop QTc greater than 500 ms or greater than or equal to 60 ms change from baseline with Torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia, otherwise temporarily suspend and dose reduce XALKORI as indicated. Bradycardia: Symptomatic bradycardia can occur in patients receiving XALKORI. Across clinical trials, bradycardia with a heart rate less than 50 beats per minute occurred in 11% of patients treated with XALKORI (n=1174). Monitor heart rate and blood pressure regularly. Avoid using XALKORI in combination with other agents known to cause bradycardia to the extent possible. Permanently discontinue for life-threatening bradycardia due to XALKORI; however, if associated with concomitant medications known to cause bradycardia or hypotension, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If concomitant medications can be adjusted or discontinued, restart XALKORI at 250 mg once daily with frequent monitoring. Otherwise temporarily suspend and resume or dose reduce XALKORI as indicated. Embryofetal Toxicity: XALKORI can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving XALKORI. If the patient or their partner becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus. Adverse Reactions: Safety was evaluated in a phase 3 study in patients with ALK-positive metastatic NSCLC randomized to XALKORI (n=172) or chemotherapy (n=171). Serious adverse reactions were reported in 37.2% patients treated with XALKORI. The most frequent serious adverse reactions reported in patients treated with XALKORI were pneumonia (4.1%), pulmonary embolism (3.5%), dyspnea (2.3%), and ILD (2.9%). Fatal adverse reactions in XALKORI-treated patients occurred in 9 (5%) patients, consisting of: acute respiratory distress syndrome, arrhythmia, dyspnea, ILD, pneumonia, pneumonitis, pulmonary embolism, respiratory failure, and sepsis. Common adverse reactions occurring in ≥25% included vision disorder (diplopia, photophobia, photopsia, vision blurred, visual acuity reduced, visual impairment, vitreous floaters), diarrhea, nausea, vomiting, constipation, edema, decreased appetite, fatigue, upper respiratory infection, and dysgeusia. Grade 3 or 4 events occurring at a higher incidence with XALKORI than with chemotherapy and at greater than 2% incidence were syncope (3%), QT prolongation (3%), and pulmonary embolism (5%). Elevation of ALT of any grade occurred in 76% of patients and grade 3 or 4 in 17% of patients. Neutropenia of any grade occurred in 49% of patients and grade 3 or 4 in 12% of patients. Lymphopenia of any grade occurred in 51% of patients and grade 3 or 4 in 9% of patients. Renal cysts occurred in 4% and neuropathy in 19% of patients treated with XALKORI. Drug Interactions: Exercise caution with concomitant use of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may increase plasma concentrations of crizotinib. Avoid concomitant use of strong CYP3A inducers and inhibitors. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. Nursing Mothers: Given the potential for serious adverse reactions in nursing infants, consider whether to discontinue nursing or discontinue XALKORI. Hepatic Impairment: XALKORI has not been studied in patients with hepatic impairment. As crizotinib is extensively metabolized in the liver, hepatic impairment is likely to increase plasma Crizotinib concentrations. Use caution in patients with hepatic impairment. Renal Impairment: Administer XALKORI at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment (CLcr<30 mL/min) not requiring dialysis. No starting dose adjustment is needed for patients with mild and moderate renal impairment. For more information and full prescribing information, please visit www.XALKORI.com About Pfizer Oncology Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide. Our strong pipeline of biologics and small molecules, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time. For more information, please visit www.Pfizer.com. DISCLOSURE NOTICE: The information contained in this release is as of March 25, 2014. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information that involves substantial risks and uncertainties regarding XALKORI (crizotinib), including its potential benefits, and about the PROFILE 1014 trial. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; uncertainty concerning the commercial impact of the outcome of the PROFILE 1014 trial; whether and when regulatory submissions may be made for XALKORI for the first-line treatment of patients with ALK-positive, advanced, non-small cell lung cancer in jurisdictions in which that indication has not been approved, and whether and when regulatory authorities in such jurisdictions will approve any such submissions, as well as their decisions regarding labeling and other matters that could affect the availability and commercial potential of that indication for XALKORI in those jurisdictions; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2013 and in its subsequent reports on Form 10-Q and Form 8-K. 1 Pfizer data on file. 2 Pfizer data on file. 3 The International Agency for Research on Cancer, the World Health Organization, GLOBOCAN 2008, Available at: http://globocan.iarc.fr/Pages/fact_sheets_population.aspx (select “World” from the drop-down menu). Accessed August 8, 2013. 4 Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: 215–224. 5 Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3: 215–224. 6 Yang P, Allen MS, Aubry MC, et al. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest.2005;128(1):452–462. 7 American Cancer Society. Detailed Guide: Lung Cancer (Non-Small Cell). Available at: http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-survival-rates. Accessed October 14, 2013.
Pfizer Inc. announced today that PROFILE 1014, a Phase 3 study of anaplastic lymphoma kinase (ALK) inhibitor XALKORI ® (crizotinib), met its primary objective of significantly prolonging progression-free survival (PFS) in previously untreated patients with ALK-positive advanced non-squamous non-small cell lung cancer (NSCLC) when compared to standard platinum-based chemotherapy regimens. PROFILE 1014 is the second positive global Phase 3 study that evaluated XALKORI against chemotherapy, a standard of care for patients with advanced NSCLC. “The results of the PROFILE 1014 study are important in that they demonstrate, for the first time, that XALKORI is superior to standard chemotherapy doublet regimens in prolonging survival without progression as first-line treatment for patients with ALK-positive advanced NSCLC,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. “These findings build upon the data from the PROFILE 1007 randomized Phase 3 study in previously treated patients and collectively establish XALKORI as a standard of care in both the first and second-line setting for patients with ALK-positive advanced NSCLC.” No unexpected safety issues were identified in the PROFILE 1014 study. The adverse events were consistent with the known safety profile for XALKORI. Efficacy and safety data from this study will be submitted for presentation at a future medical meeting. “These data from the PROFILE 1014 study highlight the importance of not only testing a tissue specimen for the presence of biomarkers at the time of diagnosis in all patients with advanced stage NSCLC, but actually having those results in hand before determining the most appropriate treatment option for each patient,” said Professor Tony Mok, Li Shu Fan Medical Foundation Professor of Clinical Oncology at the Chinese University of Hong Kong. “It is clear that a multidisciplinary collaborative approach to molecular testing is required in order to deliver those results on time, which in fact is the foundation of personalized medicine in lung cancer.”