38P Real-world treatment patterns and effectiveness of subsequent treatments following first-line (1L) brigatinib for patients with anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) from ALTA-1L

Brigatinib, an ALK tyrosine kinase inhibitor (TKI), showed superior clinical efficacy in 1L for ALK+ NSCLC compared to crizotinib in the phase III ALTA-1L trial. There is a lack of data on real-world treatment patterns and outcomes post-1L brigatinib. This non-interventional, multicenter, retrospective chart review study included patients with ALK+ NSCLC previously enrolled in the brigatinib arm of ALTA-1L. Patients who discontinued 1L brigatinib (index event) were followed from the last dose of brigatinib. Time to treatment discontinuation (TTD), progression-free survival (PFS) for the 2L therapy, time from randomization of ALTA-1L to the date of disease progression on 2L therapy or death (PFS2), and overall survival (OS) were estimated using Kaplan-Meier methods. As of Oct 18, 2023, 48 patients (median age=58 years; male=45.8%; White=43.8%; Asian=54.2%) were enrolled with a median follow-up of 12.4 months. 40 (83.3%) had received subsequent systemic anticancer therapies. Of these, 30 (75%) had received 2L ALK TKIs: 16 (53%) had received lorlatinib, 8 (27%) had received alectinib, 6 (20%) had received crizotinib. Overall response rate and disease control rate for 2L ALK TKIs were 33.3% and 70.8%, respectively, and for 2L lorlatinib were 30.8% and 76.9%, respectively. Median PFS (95% CI) was 16.1 (4.4, NR) months with an estimated 24-month PFS of 47% (26.2, 65.3) for 2L ALK TKIs, while median PFS was 25.6 (3.8, NR) months with an estimated 24-month PFS of 53.4% (23.9, 76.0) for 2L lorlatinib. Please see Table for TTD, PFS, PFS2, and OS in 2L.Table: 38PTTD, PFS, PFS2, and OS in patients with 2L ALK TKIsOutcome (95% CI)2L ALK TKIs (n=30)2L lorlatinib (n=16)mTTD, mo34.7 (4.6, NR)37.2 (6.0, NR)Receiving 2L at 24 mo, %53.1 (32.2, 70.2)68.1 (35.4, 86.8)mPFS, mo16.1 (4.4, NR)25.6 (3.8, NR)24-mo PFS, %47 (26.2, 65.3)53.4 (23.9, 76.0)mPFS2, mo51.6 (25.9, NR)74.7 (25.9, NR)24-mo PFS2, %78.4 (58.1, 89.7)86.7 (56.4, 96.5)mOS, mo74.7 (30.0, NR)74.7 (30.0, NR)36-mo OS, %66.7 (46.9, 80.5)75.0 (46.3, 89.8)2L, second line; ALK, anaplastic lymphoma kinase; CI, confidence interval; mo, month; mOS, median overall survival; mPFS, median progression-free survival; mTTD, median time to treatment discontinuation; NR, not reached; TKI, tyrosine kinase inhibitor. Open table in a new tab 2L, second line; ALK, anaplastic lymphoma kinase; CI, confidence interval; mo, month; mOS, median overall survival; mPFS, median progression-free survival; mTTD, median time to treatment discontinuation; NR, not reached; TKI, tyrosine kinase inhibitor. Most patients started another ALK TKI after discontinuing 1L brigatinib. ALK TKIs offered clinical benefit after 1L brigatinib, suggesting brigatinib is an effective 1L treatment choice followed by other ALK TKIs, including lorlatinib.