Abstract 11509 covers 107 pediatric patients and their tumors. ALK alterations were found in 18 of them (not all are fusion mutations). The ages ranged from 3-16 years. 7 patients were still being treated at the data cut off. At least 4 types of cancer were treated. To quote the abstract “Crz was well tolerated” and “children can benefit from crz therapy.” I am not a doctor so I can not compare these patients side effect profile with other similar studies. Among the 8 evaluable patients there was one complete response, 3 partial responses, and 1 stable disease (for a DCR of 5/8 (62.5%)).
Abstract 9064 covers 85 patients but only 8 patients has ALK mutations and baseline biopsies collected within 14 days of progression . L1196M was most common. The study indicated that Ceritinib was potent against several known ALK mutations.
Abstract e20643 is only available online. In this trial, 10,000 solid cancer patients blood were tested by Guardian360 (a method that sequences compete exons (the part of the DNA that encodes for proteins)). Of those patients ALK fusions were detected in 6%. EML4 was the fusion partner in 81% of the patients and 4 other fusion partners made up the rest of the 19%. 24 patients has ALK+ NSCLC. Mutant alleles ranged from 0.06% to 12.5%. They found several Somatic mutations (SNV) of which 10% were known resistance mutations in ALK. They also found other occurring SNV in other genes that are rare or absent in untreated patients suggesting possible novel Crizotinib resistance mechanisms.
Abstract 9008 covers the J-ALEX phase 3 trial comparing Crizotinib (arm A) with Alectinib (arm B) in TKI naive patients. There were 207 patients at 41 centers in Japan randomized between the two arms.
Arm A had a median PFS of 10.2 months.
Arm B median PFS was not reached.
The trial was stopped early because an independent committee recommended the release of data because the superiority of PFS had been demonstrated.
there is another international trial ongoing.
Abstract 9007 covers the Phase 2 trial (ALTA) comparing two dosing schemes. There were 222 patients who had progressed on Crizotinib. Results where as of 12-7-15.
Arm A received 90 mg straight through. Arm Breceived 90 mg for the first 7 days then received 180 mg from then on.
Arm A had ORR of 46% including 1 confirmed complete response, median PFS was 8.8 months. There were 3% discontinuations and 7% dose reductions.
Arm B had ORR of 54% including 5 confirmed complete responses, median PFS was 11.1 months. There were 6% discontinuations and 18% dose reductions.
While there were 6% (3% > or = grade 3 ) of early onset pulmonary events within the first 7 days after original dosing. However there were no such events during the first 7 days of increasing the dose to 180 mg.
the data will be updated at the oral presentation.
So there are actually 128 different abstracts that use the term ALK in either the body or the title of the abstract. I can not look at all of them. If you want to look them over you can go to abstract.asco.org
I will be summarizing the ones that I find that appear to be of general interest.
To access the database containing the abstracts go to http://abstract.asco.org/176/IndexView_176.html
Entrectinib was tested in 119 patients with three kinds of mutations: NTRK+, ALK, and ROS1. Efficacy data was reported for 24 patients.
For ALK there appear to have been 5 patients, and 57% of them had a tumor response (presumably not all partial responses). The article said “‘This response is comparable to Crizotinib,’ Dr Gandhi said ‘With the next generation of ALK inhibitors likely to replace Crizotinib, the bar is set high for targeting ALK,’ she added.'”.
For ROS1 the overall response rate was 86% (12 of 14) (presumably not all partial responses).
For NTRK+ the overall response rate was 100% (5 of 5) (presumably not all partial responses).
There are plans to conduct a phase 2 trial now that the MTD has been defined.