Depth of target lesion response to brigatinib and its association with outcomes in patients with ALK+ NSCLC in the alta trial

Background: Depth of target lesion response to crizotinib has been associated with overall survival (OS) (J ClinOncol 2016;34:abstract 2590). ALTA (NCT02094573) is an ongoing randomized phase 2 trial of brigatinib, an ALK inhibitor, in crizotinib‐refractory advanced ALK+ NSCLC patients. As the ALTA primary endpoint of confirmed objective response rate (cORR), a binary outcome, might not fully capture clinical benefit, we examined the association of maximum decrease in target lesions with progression‐free survival (PFS) and OS. Method: Patients were randomized to receive brigatinib at 90 mg qd (arm A; n=112) or 180 mg qd with a 7‐day lead‐in at 90 mg (arm B; n=110). Arms were pooled in this analysis. Patients with any target lesion shrinkage were sorted into 4 groups based on greatest decrease from baseline per RECIST v1.1; outcomes in these groups were compared with outcomes in patients with no shrinkage. Result: As of February 21, 2017, cORR in arm A/B (ITT population) was 46%/55% per investigators. 201/222 patients had ≥1 evaluable response assessment with 18.4‐month median follow‐up. Median age of these patients was 53 years; 57% were female. Patients with target lesion shrinkage (vs none) had numerically longer PFS (hazard ratios [95% CIs]: 0.61 [0.30‐1.22], 1%‐25% shrinkage; 0.47 [0.24‐0.91], 26%‐50%; 0.54 [0.28‐1.05], 51%‐75%; 0.30 [0.15‐0.63], 76%‐100%) and numerically higher estimated 1‐year OS (Table). In a multivariable analysis, 76%‐100% shrinkage (vs none) was independently associated with longer PFS/OS (hazard ratios [95% CIs]: 0.37 [0.18‐0.76]/0.35 [0.14‐0.89]); arm B (vs A) was independently associated with longer PFS. Conclusion: In this exploratory post hoc analysis, brigatinib‐treated patients with target lesion shrinkage, including those without confirmed partial response, had improved PFS/OS vs patients without shrinkage. Patients with the deepest response (76%‐100% shrinkage) appeared to have the longest PFS and higher estimated 1‐year OS. (Table Presented).