Yi-Long Wu1, Shun Lu2, You Lu3, Jianying Zhou4, Yuan-Kai Shi5, Virote Sriuranpong6, James C M Ho7, Choo Khoon Ong8, Chun-Ming Tsai9, Chin-Hee Chung10, Keith D Wilner11, Yiyun Tang11, Elizabeth T Masters10, Paulina Selaru11, Tony S Mok12. 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.
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.
RCT Entities:
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.
Authors: Fabienne Englmeier; Annalen Bleckmann; Wolfgang Brückl; Frank Griesinger; Annette Fleitz; Klaus Nagels Journal: J Cancer Res Clin Oncol Date: 2022-05-09 Impact factor: 4.553
Authors: Jose M Pacheco; Dexiang Gao; Derek Smith; Thomas Purcell; Mark Hancock; Paul Bunn; Tyler Robin; Arthur Liu; Sana Karam; Laurie Gaspar; Brian Kavanagh; Chad Rusthoven; Dara Aisner; Robert Doebele; D Ross Camidge Journal: J Thorac Oncol Date: 2018-12-30 Impact factor: 15.609