Second line settingr
The most common adverse events with crizotinib were vision disorder, diarrhoea, nausea, vomiting, constipation, elevated liver aminotransferase levels, oedema, upper respiratory infection, dysgeusia and dizziness. The majority of these events were mild (Grade 1 or 2), with the exception of elevated aminotransferase levels (Grade 3 or 4).
Grade 3 or 4 events occurred with similar incidence in both the crizotinib and chemotherapy groups (33% and 32% respectively). Treatment related serious adverse events were also similar (12% for crizotinib, 14 for chemotherapy). Permanent discontinuation secondary to adverse events occurred in 6% of those receiving crizotinib, and 10% of those receiving chemotherapy.
In those receiving crizotinib, 13% developed Grade 3 or 4 neutropenia, including one incident of febrile neutropenia. In the chemotherapy group, 19% developed Grade 3 or 4 neutropenia, with 16 cases of febrile neutropenia.
Three treatment-related deaths occurred in the crizotinib group: one attributed to ventricular arrhythmia, and two to interstitial lung disease or pneumonitis. Hepatic dysfunction developed in one patient, who died of hepatic failure after the data cut off date.
© New Engl J Med 2013
First line settingr
The most common adverse effects associated with crizotinib therapy were visual disorder (71% of patients), diarrhoea (61%) and oedema (49%). The relative incidence of fatigue, anaemia and neutropenia was significantly greater in the chemotherapy group.
Most adverse events in both groups were grade 1 or 2 in severity. Grade 3 or 4 elevations in ALT levels occurred in 11% of patients receiving crizotinib, and 2% of those in the chemotherapy group. these elevations were primarily managed by way of dose interruptions or reductions. No deaths from hepatic dysfunction occurred, however four patients were permanently discontinued from crizotinib therapy following hepatic events.
Grade 3 or 4 neutropenia occurred in 11% of patients receiving crizotinib, and in 15% of those receiving chemotherapy. no events of febrile neutropenia occurred in the crizotinib group with two cases in the chemotherapy group.
There was one treatment-related cause of death- fatal pneumonitis - attributed to crizotinib. A further two patients in the crizotinib group had their treatment permanently discontinued due to pneumonitis.