Abstract 9059 basically flung that administrating an HSP90 inhibitor at the same time as Crizotinib did not delay the development of resistance to Crizotinib.
Abstract 9061 pooled data from two clinical trials. 129 patients had biopsies done after Crizotinib but before Alectinib. Plasma samples were available for all 272 patients at baseline and for about 50% at progression.
At baseline 13 functional ALK mutations were identified (5 previously unreported). At progression 3 new mutations were seen. At least 7 baseline mutations had median PFS greater than 3 months suggesting Alectinib was active against them. Mutations I1171S/N ans G1202R may occur during treatment.
As for liquid biopsy, “Tumor DNA in plasma may be a non-invasive way to monitor resistance mutations”.
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.