[JM Article 1] ALK+ NSCLC: Real-world patterns and outcomes of treatment after 1L brigatinib

Following first-line (1L) brigatinib treatment, most patients with ALK-positive (ALK+) non-small-cell lung cancer (NSCLC) received an ALK tyrosine kinase inhibitor (TKI) as second-line (2L) therapy and experienced prolonged clinical benefit, a retrospective chart review of patients enrolled in the phase III ALTA-1L trial has shown.

ALTA-1L (n=275) evaluated the efficacy and safety of 1L brigatinib (n=137) vs crizotinib (n=138) in ALK inhibitor–naïve patients with advanced ALK+ NSCLC. At end of study, after a median follow-up of 40.4 months in the brigatinib arm and 15.2 months in the crizotinib arm, the primary endpoint of progression-free survival (PFS) by blinded independent review committee assessment reached a median of 24.0 months in the brigatinib arm vs 11.1 months in the crizotinib arm, while 3-year PFS rate was 43 percent vs 19 percent (hazard ratio [HR], 0.48; 95 percent confidence interval [CI], 0.35–0.66). Median overall survival (OS) was not reached in either group (HR, 0.81; 95 percent CI, 0.53–1.22). No new safety signals were observed. [J Thorac Oncol 2021;16:2091-2108]

The current analysis investigated real-world patterns and outcomes of 2L treatment following discontinuation of 1L brigatinib during or after completion of ALTA-1L. Data were extracted from medical records of 48 eligible patients (median age, 58 years; female, 54.2 percent; Asian, 54.2 percent; never smokers, 62.5 percent) between 4 November 2022 and 18 October 2023. [Delmonte A, et al, ELCC 2024, poster 38P]

Among the 48 patients, the most common reason for discontinuation of 1L brigatinib was progressive disease (70.9 percent). Forty patients (83.3 percent) received 2L systemic anticancer therapy at a median of 4.0 days from the last dose of brigatinib. Of these, 30 patients (75.0 percent) received an ALK TKI as 2L treatment, with the most commonly used agent being lorlatinib (n=16; 53.3 percent), followed by alectinib (n=8; 26.7 percent) and crizotinib (n=6; 20.0 percent). Median real-world time to discontinuation of 2L treatment was 34.7 months for ALK TKIs and 37.2 months for lorlatinib.

Among the 30 patients who received 2L ALK TKIs, real-world overall response rate (rwORR) was 33.3 percent and real-world disease control rate (rwDCR) was 70.8 percent. Among 16 patients who received 2L lorlatinib, rwORR was 30.8 percent and rwDCR was 76.9 percent.

“Patients who received subsequent ALK TKIs [including lorlatinib] after 1L brigatinib had prolonged clinical benefit,” the investigators reported.

Over a median follow-up of 12.4 months, median real-world PFS (rwPFS) was 16.1 months for 2L ALK TKIs and 25.6 months for 2L lorlatinib. rwPFS rates were 47.0 percent and 53.4 percent at 24 months, and 40.3 percent and 40.1 percent at 36 months, respectively.

Median rwPFS2, defined as time from randomization in ALTA-1L to first documented disease progression on 2L treatment or death, was 51.6 months in patients receiving 2L ALK TKIs and 74.7 months in those who received 2L lorlatinib. rwPFS2 rates were 78.4 percent and 86.7 percent at 24 months, and 66.7 percent and 73.3 percent at 36 months, respectively.

Median OS from date of randomization in ALTA-1L was 74.7 months in patients who received 2L ALK TKIs and the same in those who received 2L lorlatinib. OS rates were 73.3 percent and 81.3 percent at 24 months, and 66.7 percent and 75.0 percent at 36 months, respectively.

“Due to small sample size, Kaplan-Meier estimates of median require cautious interpretation, particularly given the wide CIs,” the investigators noted.