Positive Data Continue to Accrue for Crizotinib in ALK-Positive NSCLC
Stockholm, Sweden—In patients with advanced non–small-cell lung cancer (NSCLC) and anaplastic lymphoma kinase (ALK) gene rearrangements, treatment with crizotinib (Xalkori) provided clinically meaningful antitumor activity, producing responses in 51% of patients, in the multicenter phase 2 PROFILE 1005 study reported at the 2011 European Multidisciplinary Can cer Congress.
Rearrangements in ALK (ie, activating ALK mutations or translocations) are seen in up to 5% of patients, and crizotinib—a first-in-class, oral, potent, and selective small molecular entity— competitively inhibits ALK.
The report was based on an ongoing open-label phase 2 study of the first 133 evaluable patients, who received crizotinib 250 mg twice daily on a continuous basis until progression. Objective responses were observed in 50.4% of patients, with 1 being a complete response. Stable disease was observed in another 33.8%, reported Dong-Wan Kim, MD, Clinical Researcher, Seoul National University Hospital, South Korea.
Of all responders, 79.4% demonstrated a response within the first 8 weeks of treatment and maintained it for an average of 42 weeks. A total of 32% of patients discontinued the study, but only 4.4% as a result of adverse events. Treatment-related grade 3-4 adverse events were reported in 26% of patients, mainly elevated liver enzymes and neutropenia.
About half the patients completed patient-reported outcomes for key symptoms and global quality of life. Clinically meaningful improvements (change, ≥10 points) were reported for pain, dyspnea, and cough from as early as cycle 2 and for fatigue from cycle 5; these positive changes were maintained through all subsequent cycles. Global quality of life was also maintained during treatment, with clinically meaningful improvement seen by cycle 7, Dr Kim reported.
Visual Effects Evaluated
One of the most frequently reported side effects of crizotinib treatment is visual events. These are described as image carryover, flashing/trailing lights and floaters, and/or blurry vision, often occurring during light adaptation. A patient-reported questionnaire (Visual Symptom Assessment Questionnaire [VSAQ]) was developed to further characterize these symptoms and their effect on activities of daily living. Ben Solomon, MD, of the Peter MacCallum Cancer Centre, located in Mel bourne, Australia, reported a preliminary analysis of VSAQ findings in 57 patients, showing that the visual effects associated with crizotinib had no or only minimal impact on patients’ daily activities.
“The majority of patients reported that each visual effects event was transient, lasting either 30 seconds or less or between 30 and 60 seconds,” Dr Solomon noted. Approximately 56% of patients at cycle 2 and 50% at cycle 3 and cycle 4 reported visual effects, but these did not require dose alterations, he said. The frequency of visual effects varied during cycles 2 to 4. Most patients said they were not bothered by the visual effects events or found them “only a little bothersome,” Dr Solomon said. No clinically meaningful changes were noted on ophthal mic examinations. —CH