ALTA trial has evaluated 2 doses of the ALK inhibitor Brigatinib post-Crizotinib. Overall objective response rate ( ORR ) contains both CNS and extra-CNS target lesion data.
In ALTA, stratification included baseline CNS disease ( +/− ). Patients were randomized to Brigatinib 90 mg qd ( arm A ) or 180 mg qd with a 7-day lead-in at 90 mg ( arm B ).
To differentiate CNS and extra-CNS efficacy researchers have compared CNS ORR with overall ORR by baseline CNS status.
222 patients were randomized ( n=112/110, arm A/B ); 71% / 67% had baseline CNS lesions.
Of 247/204 total target lesions in A/B, 38 ( 15% ) and 32 ( 16% ), respectively, were in the CNS; 28 ( 25% ) patients in A and 23 ( 21% ) in B had greater than or equal to 1 target CNS lesion.
Median follow-up was 19.6/24.3 months.
Per independent review, CNS ORR in patients with measurable baseline CNS lesions ( n=26/18, A/B ) was 50% / 67%; in patients with any baseline CNS lesions ( n=81/74, A/B ), median intracranial progression-free survival ( iPFS ) was 12.8 / 18.4 months.
Dose reductions or discontinuations due to adverse effects ( A/B ): 7% / 29% and 4% / 11%.
In conclusions, with more than 24 months follow-up, the recommended Brigatinib 180 mg dose ( with lead-in ) continues to demonstrate long PFS and iPFS and high CNS ORR.
Comparable CNS ORR ( 67% ) and overall ORRs in patients with ( 61% ) or without ( 55% ) baseline CNS target lesions support Brigatinib’s broad whole-body activity. ( Xagena )
Source: American Society of Clinical Oncology - ASCO Meeting, 2018