Abstract
ABSTRACT Background Crizotinib is a potent, small-molecule ALK inhibitor with a high response rate in advanced ALK-positive NSCLC. In early phase studies, patients (pts) commonly reported mild visual disturbances. Here we characterize such visual effects with objective and subjective measures in an ongoing phase II study (PROFILE 1005). Methods Previously treated pts with advanced ALK-positive NSCLC received crizotinib 250 mg BID. Ophthalmological examinations, comprising best corrected visual acuity (BCVA), biomicroscopy, and fundoscopy, were performed at screening and after a visual effect event was reported, except for a subset of pts in France, where examinations were done every 4 cycles. In addition, on day 1 of each cycle, pts completed the Visual Symptom Assessment Questionnaire (VSAQ) that assessed the presence, frequency, timing, duration, and severity of visual effects and their impact on activities of daily living (ADL). Results As of Jan 2012, 901 pts had enrolled in PROFILE 1005; 21 - 27% were evaluable for ophthalmological examinations (visual acuity: 193/901; biomicroscopy: 239/901; fundoscopy: 239/901). There were no changes in BCVA, conjunctiva, cornea, anterior chamber, iris, lens, or fundus attributable to crizotinib. The most frequently reported ophthalmological finding was worsening of cataracts (right eye: 9%; left eye: 10%), which was not attributed to crizotinib. Visual effects as identified by the VSAQ were reported by 65% of pts (405/622) at cycle 2 (C2), 58% at C3 (323/558), 55% at C4 (287/519), and 50% at C5 (247/495). The most common were appearance of flashing lights, streamers/strings/floaters, and overlapping shadows. Most pts reported each event as lasting ≤1 min (C2: 63%; C3: 68%; C4: 72%; C5: 75%), occurring mostly in the morning (46–59%) and/or evening (70–74%). The majority of pts reported that visual effects were not at all or a little bothersome, with no or minimal impact on ADL. Similar results were observed in the French pt subset. Conclusions There were no objective ophthalmological changes associated with the visual effects on crizotinib. Pt-reported visual effects were frequent, but transient, with no or minimal impact on ADL. Disclosure B. Besse: Research funding: Pfizer. B. Solomon: Compensated advisory relationship: Pfizer. Research funding: Pfizer. A. Shaw: Compensated advisory relationship: Pfizer, Ariad, Chugai, Novartis, and Daiichi-Sankyo. Research funding: AstraZeneca and Novartis. D. Kim: Compensated advisory relationship: Pfizer. Honoraria: Pfizer. R. Schachar: Compensated employment: Pfizer. Stock ownership: Pfizer. K. Wilner: Compensated employment: Pfizer. Stock ownership: Pfizer. A. Reisman: Compensated employment: Pfizer. Stock ownership: Pfizer. C.H. Bartlett: Compensated employment: Pfizer. Stock ownership: Pfizer. S. Iyer: Compensated employment: Pfizer. All other authors have declared no conflicts of interest.
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