Positive Data Continue to Accrue for Crizotinib in ALK-Positive NSCLC

In patients with advanced non–small cell lung cancer (NSCLC) with ALK gene rearrangements, treatment with crizotinib provided clinically meaningful antitumor activity, producing responses in 51% of patients, in a multicenter phase 2 study reported at the 2011 European Multidisciplinary Cancer Congress.

Rearrangements in ALK 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 data from the first 133 evaluable patients who received crizotinib 250 mg twice daily on a continuous basis until progression in an ongoing open-label phase 2 study. Objective responses were observed in 50.4% of patients, one being a complete response. Stable disease was observed in another 33.8%, reported Dong-Wan Kim, MD, Clinical Researcher at Seoul National University Hospital in South Korea.

Among the responders, 79.4% de m - onstrated a response within the first 8 weeks of treatment and maintained the response for an average of 42 weeks. Although 32% of patients discontinued the study, only 4.4% did so as a result of adverse events. Treatment-related grade 3/4 adverse events, mainly elevated liver enzymes and neutropenia, were reported in 26% of patients.

About half the patients completed patient-reported outcomes for key symptoms and global quality of life. Clinically meaningful improvements (≥10-point change) were reported for pain, dyspnea, and cough from as early as cycle 2, and for fatigue, cycle 5; these positive changes were maintained through subsequent cycles. Global quality of life was also maintained over treatment, with clinically meaningful improvement seen by cycle 7, Kim reported.

One of the most commonly reported side effects of treatment with crizotinib 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.

At the meeting, Ben Solomon, MD, of Peter MacCallum Cancer Centre in Melbourne, 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’ activities of daily living in the ongoing PROFILE 1005 study of the drug.

“The majority of patients reported that each visual effects event was transient, lasting either 30 seconds or less or between 30 and 60 seconds,” 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. In cycle 2, most patients reported visual effects on multiple days per week, whereas during cycles 3 and 4 most patients reported visual effects no more than once a week.

Most patients experienced these events in the morning or evening, rather than midday. Most patients said they were not bothered by the visual effects events or found them “only a little bothersome,” Solomon said. Patients did not have regular difficulty seeing at night or adapting to changes in lighting. No clinically meaningful changes were noted on ophthalmic examinations.