Results of PROFILE 1029, a Phase III Comparison of First-Line Crizotinib versus Chemotherapy in East Asian Patients with ALK-Positive Advanced Non-Small Cell Lung Cancer

Wu YL 1 , Lu S 2 , Lu Y 3 , Zhou J 4 , Shi YK 5 , Sriuranpong V 6 Show all authors , Ho JCM 7 , Ong CK 8 , Tsai CM 9 , Chung CH 10 , Wilner KD 11 , Tang Y 11 , Masters ET 10 , Selaru P 11 , Mok TS 12

Affiliations 

  • 1 Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China. Electronic address: syylwu@live.cn
  • 2 Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Jiao Tong University, Shanghai, People's Republic of China
  • 3 Department of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
  • 4 Respiratory Department, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
  • 5 Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
  • 6 Medical Oncology Unit, Department of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  • 7 Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China
  • 8 Department of Respiratory Medicine, Hospital Pulau Pinang, Pulau Pinang, Malaysia
  • 9 Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
  • 10 Pfizer Oncology, New York, New York
  • 11 Pfizer Oncology, La Jolla, California
  • 12 Department of Clinical Oncology, State Laboratory of South China, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
J Thorac Oncol, 2018 10;13(10):1539-1548.
PMID: 29966800 DOI: 10.1016/j.jtho.2018.06.012

Abstract

INTRODUCTION: The phase III randomized PROFILE 1014 study demonstrated superiority of crizotinib to first-line chemotherapy in prolonging progression-free survival (PFS) in previously untreated patients with ALK receptor tyrosine kinase gene (ALK)-positive advanced nonsquamous NSCLC. This result was consistent with that in the smaller subset of East Asian patients in PROFILE 1014. The subsequent study reported here prospectively evaluated crizotinib in a larger East Asian patient population.

METHODS: In this open-label phase III study (PROFILE 1029), patients were randomized 1:1 to receive orally administered crizotinib 250 mg twice daily continuously (3-week cycles) or intravenously administered chemotherapy (pemetrexed 500 mg/m2, plus cisplatin 75 mg/m2, or carboplatin [at a dose to produce area under the concentration-time curve of 5-6 mg·min/mL]) every 3 weeks for a maximum of six cycles. PFS confirmed by independent radiology review was the primary end point.

RESULTS: Crizotinib significantly prolonged PFS (hazard ratio, 0.402; 95% confidence interval [CI]: 0.286-0.565; p < 0.001). The median PFS was 11.1 months with crizotinib and 6.8 months with chemotherapy. The objective response rate was 87.5% (95% CI: 79.6-93.2%) with crizotinib versus 45.6% (95% CI: 35.8-55.7%) with chemotherapy (p < 0.001). The most common adverse events were increased transaminase levels, diarrhea, and vision disorders with crizotinib and leukopenia, neutropenia, and anemia with chemotherapy. Significantly greater improvements from baseline in patient-reported outcomes were seen in crizotinib-treated versus chemotherapy-treated patients.

CONCLUSIONS: First-line crizotinib significantly improved PFS, objective response rate, and patient-reported outcomes compared with standard platinum-based chemotherapy in East Asian patients with ALK-positive advanced NSCLC, which is similar to the results from PROFILE 1014. The safety profiles of crizotinib and chemotherapy were consistent with those previously published.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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