Overall, I would say the results were disappointing, fewer patients had progressed far enough for meaningful results than I had hoped for. However, given that the data cut offs were usually around December and most of the trials were near the end of phase 1, hopefully updated results at ASCO will be more revealing. There were positive initial results on brain metastases for Alectinib, and AP26113. X396 had a higher partial response rate of 83% at it highest two doses, but only 6 patients were in that category. Several drugs had initial responses with cancers other than NSCLC.
Here is the link were you can search for the abstracts: abstsearch.asco.org/144_60057/search.php?zoom_sort=0&zoom_query=ALK+inhibitors&zoom_per_page=50&zoom_and=1
There is an update on Ceritinib. It is besed on 255 patients, 246 were ALK+ NSCLC. 67% had received greater than or equal to 2 prior anti cancer therapies. Otbjective response rates were equal to or were better than 60% for each subgroup of patients who had 0,1,2, and 3 prior anti cancer treatments.
The following data is for 180 patients who had received greater than 18 weeks of treatment prior to AUG. cutoff.
The most common adverse events continued to be GI related and fatigue.
For Crizotinib resistant patients the objective (+30%) response rates (ORR) were 55% and the progression free survival (PFS) median period was 6.9 months.
For Crizotinib naive the ORR was 69.5% and the median PFS was not estimated. However the PFS at 12 months was 58.1%.
There is an update for AP26113 with 114 patients. 65 in phase 1 and 49 in phase 2. The most common adverse events were GI related, fatigue and headaches. Adverse events were generally lower than in Ceritinib.
Early onset pulmonary symptoms requiring immediate medical attention happened in 13% of patients at 180mg. None of these symptoms happened in patients at 90mg. So they changed the protocol. Half of the patients will get one week at 90mg and then step it up to 180mg. The other half will start with and stay at 90 mg. I believe that since the changed the protocol, no more early onset pulmonary symptoms have occurred.
Of 38 evaluable ALK+ NSCLC patients with prior Crizotinib there was an ORR of 63%. Duration of response was between 1.6 months and 14.7 months (ongoing). Among 42 evaluable patients median PFS is 47 weeks.
There were 10 patients with untreated brain metastases. 6 had responses in the brain including 4 with undetectable brain mets after treatment.