P45.09 Real-World Sequencing of ALK-TKIs in Advanced Stage ALK-positive NSCLC patients in Canada

Abstract

Overall survival (OS) of patients with ALK+ Non-Small Cell Lung Cancer (NSCLC) has been prolonged with the introduction of ALK-tyrosine kinase inhibitors (TKI) over the last decade. The aim of this analysis was to study treatment patterns, sequencing of ALK-TKIs and outcomes in a real-world cohort of ALK+ NSCLC patients. Data were analyzed for all patients with advanced/metastatic ALK+ NSCLC seen at Princess Margaret Cancer Centre (data cut-off date March 18, 2021), regardless of whether they were initially diagnosed with early stage (relapsed) or de novo advanced/metastatic NSCLC. Clinico-demographic, treatment and survival data were collected retrospectively. Of 147 patients with advanced/metastatic ALK+ NSCLC, 32 were initially early-stage, while 115 were de novo advanced/metastatic. The median age was 59 years (range: 31 – 93); 84 (57%) were female; 111 (76%) were never-smokers; 32 (22%) had an ECOG performance status (PS) of 0, while 78 (55%) were PS1, and 33 (23%) were PS2+; 54 (47%) were Asian; 40 (35%) were Caucasian. Median follow-up time was 26.9 months from diagnosis of advanced/metastatic disease. Among the 147 patients, 138 (94%) received ALK-TKIs: 66 (48%) received only one ALK-TKI, while 42 (30%) had received two; 30 (22%) had received at least three. Overall, 75 (54%) had received crizotinib; 103 (75%) alectinib; 31 (22%) ceritinib; 22 (16%) brigatinib and 27 (20%) lorlatinib. Crizotinib (74; 54%) and alectinib (59; 43%) were given as first ALK-TKI in the majority of cases, whereas ceritinib, brigatinib and lorlatinib mainly were administered after failure of previous ALK-TKI and/or other systemic therapy in 26 (31%) in second-line, 25 (30%) in third-line, 12 (15%) in fourth-line, and 17 (21%) in fifth-line or beyond. Median progression-free survival irrespective of treatment line given was 9 months for crizotinib, 41.6 months for alectinib, 3.1 months for ceritinib, 3.7 months for brigatinib and 2.8 months for lorlatinib. Unlike clinical trials, brigatinib and lorlatinib were given often in PS 2+ patients near end-of-life or as fourth or fifth-line treatment. After removing such patients, median PFS was 7.1 (95%CI 1.8-NA) for brigatinib and 7.2 (95%CI 1.4-NA) for lorlatinib. Median overall survival (OS) from advanced/metastatic disease was 56.7 months, but is likely to increase as the first-line alectinib cohort matures. Median OS for patients treated first-line with crizotinib was 46.1 months, and not yet reached in patients treated with first-line alectinib. A total of 31 (21%) patients died within two years of diagnosis of advanced/metastatic disease. These patients did not significantly differ in age, sex or PS from patients with prolonged survival. Of these patients, 6 (19%) never received an ALK-TKI, but the majority received two lines (21; 68%) of ALK-TKI treatment. Sequencing of multiple ALK-TKIs has improved outcomes, but there is no single sequencing standard. Use of next generation ALK-TKIs in earlier lines of treatment may lead to more effective outcomes. Despite substantial progress, approximately 20% of patients still do poorly; identification of novel drug resistance mechanisms may further improve outcomes.