Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Poster Discussion Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 7533)
Dong-Wan Kim, Myung-Ju Ahn, Yuankai Shi, Tommaso Martino De Pas, Pan-Chyr Yang, Gregory J. Riely, Lucio Crinò, Tracey L. Evans, Xiaoqing Liu, Ji-Youn Han, Ravi Salgia, Denis Moro-Sibilot, Sai-Hong Ignatius Ou, Scott N. Gettinger, Yi Long Wu, Silvana Lanzalone, Anna Polli, Shrividya Iyer, Alice Tsang Shaw; Seoul National University Hospital, Seoul, South Korea; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Medical Oncology Unit of Respiratory Tract and Sarcomas, New Drugs Development Division, European Institute of Oncology, Milan, Italy; National Taiwan University Hospital, College of Medicine, Taipei, Taiwan; Memorial Sloan-Kettering Cancer Center, New York, NY; Azienda Ospedaliera di Perugia, Perugia, Italy; Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA; 307 Hospital of the Academy of Military Medical Sciences, Cancer Center, Beijing, China; Center for Lung Cancer, National Cancer Center, Goyang, South Korea; The University of Chicago, Chicago, IL; Hôpital Universitaire, Grenoble, France; University of California, Irvine, CA; Yale University School of Medicine, New Haven, CT; Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; Pfizer Oncology, Pfizer Italia Srl, Milan, Italy; Pfizer Oncology, Milan, Italy; Pfizer Inc., New York, NY; Massachusetts General Hospital Cancer Center, Boston, MA

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Abstract Disclosures


Background: Approximately 3–5% of NSCLC harbors ALK gene rearrangements. Crizotinib is a first-in-class, oral, small-molecule competitive ALK inhibitor with anti-MET activity. Methods: PROFILE 1005 is an ongoing global, multicenter, open-label, single-arm, phase II study evaluating the safety and efficacy of crizotinib (250 mg BID in 3-week cycles) in patients with advanced ALK-positive NSCLC who progressed after ≥1 chemotherapy for recurrent/advanced/metastatic disease. Tumor response was evaluated by RECIST 1.1 every 6 weeks. Patient-reported symptoms and global quality of life (QOL) were assessed using the EORTC QLQ-C30 and LC-13 at baseline, day 1 each cycle and at end of treatment. Results: As of June 2011, 439 patients were evaluable for safety and 255 patients for tumor response. Median age was 53 years. The majority of patients were female (53%), never smokers (65%), and had adenocarcinoma (92%), ECOG PS 0–1 (83%) and ≥2 prior chemotherapy regimens (85%). Among patients evaluable for efficacy, median treatment duration was 25 weeks (77% of patients still ongoing). ORR was 53% (95% CI: 47–60), disease control rate at 12 weeks was 85% (95% CI: 80–89), median duration of response was 43 weeks (96% CI 36–50) and median PFS was 8.5 months (95% CI: 6.2–9.9). The most frequent treatment-related AEs were visual effects (50%), nausea (46%), vomiting (39%), and diarrhea (35%), mostly grade 1–2. 29 patients (6.6%) had treatment-related SAEs, including dyspnea and pneumonitis (4 patients each; 0.9%), and febrile neutropenia and renal cyst (2 patients each; 0.5%). A statistically significant (p<0.05) and clinically meaningful (≥ 10 points) improvement from baseline was observed for patient-reported overall pain, pain in chest, cough, dyspnea, insomnia, fatigue and global QOL. Conclusions: Crizotinib demonstrated a high response rate and PFS, favorable tolerability profile and improvement in patient-reported symptoms. These results provide strong evidence for crizotinib as a standard of care for advanced ALK-positive NSCLC.