Abstracts 8060, 8059, and 8058 relate to Ceritinib. Please see glossary for acronym definitions.
Abstract 8060 covers the Ascend 3 trial, which is a phase 2 trial that includes ALK inhibitor naive patients. As of 6-27-2014 the trial had 124 patients and 50 had brain mets.
For patients with no brain mets, ORR was 67.6%, DCR was 91.9%, PFS was 10.8 months. For patients with brain mets, ORR was 58%, DCR was 86%, PFS was 9.1 months.
Abstract 8059 covers the Ascend 2 trial, which is a phase 2 trial that includes patients previously treated with Crizotinib. As of the August 2014 data cutoff, there were 140 patients in the trial and 100 had brain mets.
For patients with no brain mets, ORR was 52.5%, DCR was 85%, PFS was 11.3 months. For patients with brain mets, ORR was 33%, DCR was 74%, PFS was 5.4 months.
Abstract 8058 is a different kind of study. It is an adjusted indirect comparison of Ceritinib with Crizotinib for ALK inhibitor naive patients. For Crizotinib there were 557 patients extracted from 3 different trials. For Ceritinib there were 189 patients pooled from 2 different trials. To adjust for cross trial differerences in the ethnic makeup and number of prior treatment regimens, the pool of Ceritinib patients was adjusted so all available baseline chacteristics were balanced to match the Crizotinib pool of patients.
Crizotinib patients had a PFS of 8.3 months and and the 12 month OS rate was 66%. Ceritinib patients had a PFS of 13.8 months and and the 12 month OS rate was 83%.
However this comparison does not assess which drug would be better to start on assuming a patient was to take both drugs. For example Crizotinib may not cross the blood brain barrier well but it may take the cancer an average of 8 months to do that. Meanwhile, Ceritinib may cross the blood brain barrier more easily, but it takes an average of 13 months for mutations to occur that cause resistance to form. Thus hypothetically if you took Crizotinib first you could get a combined PFS of 22.1 months. Whereas if you took Ceritinib first you could get a hypothetical combined PFS of 13.8 months. Obviously the real world is much more complicated than this hypothetical and that is why we need to do clinical trials comparing the sequencing of different drugs as well as all the other trials.
http://abstracts.asco.org/156/AbstView_156_145907.html ASCEND 3
http://abstracts.asco.org/156/AbstView_156_144861.html ASCEND 2
http://abstracts.asco.org/156/AbstView_156_143947.html Comparison with Crizotinib