Crizotinib is effective in shrinking tumors in patients with anaplastic lymphoma receptor tyrosine kinase (ALK) positive non-small cell lung cancer, a cancer commonly found in people who never smoked, and should be the standard of care for advanced stages of this disease, according to research presented at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology. This symposium is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), the International Association for the Study of Lung Cancer (IASLC) and The University of Chicago.
ALK gene rearrangements are found in around 5 percent of lung cancer tumors and are more common in people with lung cancer who never smoked. Crizotinib is an oral drug that was found to inhibit the effects of the ALK gene and to stop or reverse tumor growth.
In this phase II trial, researchers followed 901 patients for safety and 261 patients for tumor response; all of the patients had at least one prior chemotherapy treatment for their lung cancer. The overall response rate to crizotinib treatment was 60 percent and the median progression free survival (PFS) was eight months, confirming prior findings that crizotinib shrinks ALK-positive lung cancers and demonstrates a high PFS rate.
“This trial demonstrates that we have a good opportunity to shrink cancers and improve symptoms for patients with this subtype of lung cancer,” said Gregory Riely, MD, PhD, lead author of the study and a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York who specializes in treating lung cancer. “This confirms the results of prior studies and further shows that crizotinib can reduce the effects of symptoms, thereby improving the quality of life for thousands of patients who are diagnosed with this late-stage lung cancer. This study confirms that crizotinib is the standard of care for patients with ALK positive lung cancer.”
The abstract, “Results of a Global Phase II Study with Crizotinib in Advanced ALK-positive Non-small Cell Lung Cancer (NSCLC),” was presented during the Plenary Session at 12:30 p.m., Central time on September 7, 2012.
Results of A Global Phase II Study with Crizotinib in Advanced ALK-positive Non-small Cell Lung Cancer (NSCLC)
G. J. Riely1, T. L. Evans2, R. Salgia3, S. I. Ou4, S. N. Gettinger5, G. A. Otterson6, S. Lanzalone7, A. Polli8, A. T. Shaw9, 1Memorial Sloan-Kettering Cancer Center, New York, 2University of Pennsylvania, Philadelphia, 3University of Chicago, Chicago, 4University of California at Irvine, Irvine, Calif., 5Yale University School of Medicine, New Haven, Conn., 6The Ohio State University, Columbus, Ohio, 7Pfizer Italy Srl, Milan, Italy, 8Pfizer Inc., Milan, Italy, 9Massachusetts General Hospital Cancer Center, Boston
Purpose/Objective(s): 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.
Materials/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.
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%).
Conclusions: Crizotinib demonstrated a high response rate and PFS, and a favorable tolerability profile. These results provide strong evidence for crizotinib as a standard of care for advanced ALK-positive NSCLC.
Author Disclosure Block: G.J. Riely: E. Research Grant; BMS, Pfizer, Merck, GSK, Infinity. G. Consultant; Chugai, Tragara, Ariad, Daiichi, Abbott. T.L. Evans: None. R. Salgia: None. S.I. Ou: E. Research Grant; Pfizer. F. Honoraria; Pfizer. G. Consultant; Pfizer. S.N. Gettinger: E. Research Grant; Pfizer. G.A. Otterson: E. Research Grant; Pfizer, Genentech, Tragara, Amgen, Pharmacyclics. G. Consultant; Genentech, Abraxis. S. Lanzalone: A. Employee; Pfizer. K. Stock; Pfizer. A. Polli: A. Employee; Pfizer. K. Stock; Pfizer. A.T. Shaw: E. Research Grant; Novartis, Astra Zeneca, Pfizer, Ariad. F. Honoraria; Novartis, Millenium. G. Consultant; Pfizer, Ariad, Chugai, Daiichi-Sankyo.