This was reflected in patient-reported lung cancer symptoms and quality of life. Based on the EORTC Quality of Life Questionnaire (QLQ C-30) and QLQ-LC 13, crizotinib patients had greater improvement from baseline in cough, dyspnea, fatigue, alopecia, insomnia, and pain as well as global quality of life (both P less than .0001).
Patrice Wendling/IMNG Medical Media
Dr. Jean-Charles Soria
"This is a compound with very mild toxicity," commented Dr. Soria.
He said clinicians need to be aware of crizotinib’s distinct side effect profile, including other rare events such as renal cysts, pneumonitis, asymptomatic bradycardia, and low testosterone, "although we don’t really know if it impacts sexual life."
The topic of hypogonadism was raised in a separate session on second-generation ALK inhibitors at the meeting and in a recent report of rapid-onset hypogonadism secondary to crizotinib use in 19 men with metastatic NSCLC (Cancer 2012 [doi:10.1002/cncr.27450]).
Dr. Shaw said in an interview that the study was small and "requires a lot more validation." Although testosterone levels were not checked in PROFILE 1007, it is being done for the next generation of ALK inhibitors, she added.
Dr. Soria said resistance to crizotinib will become a problem with increasing worldwide use, and that strategies to counter this may include the second-generation ALK inhibitors, increased crizotinib dosing, and crizotinib plus ablative therapy given the poor penetration of crizotinib in the brain.
Brain metastases were present in 35% of patients in both arms. Three-fourths of patients were never smokers, roughly 95% had adenocarcinoma, and their median age was about 50 years.
Dr. Shaw reported an advisory relationship with Pfizer, Ariad, Chugai, Novartis, and Daiichi-Sankyo and research funding from AstraZeneca and Novartis. Dr. Soria reported consultancy fees and steering committee activities with several firms including Pfizer, which sponsored the study.