(ChemotherapyAdvisor) – The novel oral small molecule crizotinib demonstrated a high response rate in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), providing “strong evidence” the agent should be considered standard of care for this population, according to updated results of an ongoing global trial reported at the 2012 Chicago Multidisciplinary Symposium in Thoracic Oncology.

Approximately 3% to 5% of NSCLC tumors harbor ALK gene arrangements, which are more common in those who never smoked. PROFILE 1005, an open-label, single-arm phase 2 study, is evaluating the safety and efficacy of crizotinib 250mg twice daily in 3-week cycles in 901 patients with advanced ALK-positive NSCLC with disease progression after at least one prior chemotherapy regimen for recurrent advanced or metastatic disease, reported Gregory Riely, MD, PhD, lead study author and a medical oncologist at Memorial Sloan-Kettering Cancer Center, New York, NY.

Of 439 patients evaluable for safety and 255 for response as of June 2011, median age was 53 years; 53% were females and 65% never smokers; 92% had adenocarcinoma. The majority (85%) had at least 2 prior chemotherapy regimens. Median treatment duration was 25 weeks, with 77% of patients continuing treatment.

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Objective response rate was 60%: 4 patients (2%) had a complete response and 151 (58%) a partial response; 69 patients (27%) had stable disease. Median progression-free survival was 8 months (95% CI, 7–10). Disease control rate at 12 weeks was 85% (95% CI: 80–89) and median duration of response was 43 weeks (96% CI 36–50).

Crizotinib continued to show a good safety profile in patients with previously treated ALK-positive advanced NSCLC, Dr. Riely reported. The most frequent treatment-related adverse events (AEs) were primarily grade 1 or 2 visual effects (50%), nausea (46%), vomiting (39%), and diarrhea (35%). A total of 29 patients (6.6%) had treatment-related serious AEs, including dyspnea and pneumonitis (4 patients each; 0.9%), and febrile neutropenia and renal cyst (2 patients each; 0.5%).

Clinically meaningful improvement was observed in global quality of life and in lung cancer symptoms such as fatigue, cough, dyspnea, chest pain.

The symposium is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and The University of Chicago.


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