Abstract 92P
Background
For patients with ALK-positive metastatic non-small cell lung cancer (NSCLC), the recommended first-line (1L) treatment is an ALK tyrosine kinase inhibitor (TKI). Second-generation (2G; alectinib, brigatinib) or third-generation (3G; lorlatinib) TKIs are preferred versus first-generation crizotinib. This study examined real-world treatment sequencing and survival of patients treated with 1L ALK TKIs.
Methods
This retrospective cohort study utilized the Flatiron Health electronic health record-derived de-identified database of patients with ALK-positive metastatic (stage IV) NSCLC treated with 1L ALK TKIs in the United States from 01 January 2016 to 30 November 2023. Patients treated with 1L alectinib, brigatinib, crizotinib, ceritinib, or lorlatinib monotherapy between 01 November 2017 and 30 November 2021 were included. Treatment sequencing from 1L to 2L was summarized, and real-world overall survival (rwOS) and progression-free survival (rwPFS) were analyzed for patients receiving 1L alectinib. Outcomes for other 1L ALK TKIs were not analyzed due to low patient counts. Baseline patient characteristics (age, sex, race, ECOG PS, histology, and brain metastases) were adjusted to match aggregate data from the CROWN trial (NCT03052608) using propensity score weighting. Median rwOS and rwPFS were analyzed using the Kaplan-Meier method.
Results
A total of 272 patients were included, with 93% (n=252) receiving 2G TKIs, primarily alectinib (n=240, 88%). Compared to patients in the CROWN trial, the cohort was older, predominantly White, and more patients had an ECOG score of 2. Among the 240 patients treated with 1L alectinib, 42% (n=100) received 2L treatment, mainly lorlatinib (64% of 2L treatments). For patients treated with 1L alectinib, unadjusted median rwOS was 56.5 months (95% CI: 48.7-not estimable [NE]), and median rwPFS was 28.5 months (95% CI: 24.5–36.4). After propensity score weighting, median rwOS was 54.0 months (95% CI: 37.9-NE), and rwPFS was 26.8 months (95% CI: 19.6–35.8).
Conclusions
Most ALK-positive metastatic NSCLC patients received 2G TKIs (alectinib) at 1L and lorlatinib at 2L in the real-world. Adjusted rwPFS for 1L alectinib was shorter than published results from the CROWN trial (lorlatinib group).
Legal entity responsible for the study
Pfizer.
Funding
Pfizer.
Disclosure
M.F. Dietrich: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Coherus, DSI, Eli Lilly, Gilead, Johnson and Johnson, Jazz Pharmaceuticals, Merck/EMD Serono, Pfizer, Pharmacosmos, Regeneron, Stemline, Takeda; Financial Interests, Personal, Advisory Role: Bayer, Boehringer Ingelheim, Replimune, Sanofi; Financial Interests, Personal, Advisory Role, MD was a paid consultant to Pfizer in connection with the study analysis and interpretation.: Pfizer. D. Zala: Financial Interests, Personal, Other, Employed as a contractor by the organisation at the time of the study: Pfizer. D. Abrahami, J. Assayag, A. Patel: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. D. Benjumea: Financial Interests, Institutional, Funding, DB is employed by Genesis Research Group which received funds from Pfizer to conduct the study and develop the abstract.: Genesis Research Group. A. Rava: Financial Interests, Institutional, Funding, AR is employed by Genesis Research Group which received funds from Pfizer to conduct the study and develop the abstract.: Genesis Research Group. A. Crowley: Financial Interests, Institutional, Funding, AC is employed by Genesis Research Group which received funds from Pfizer to conduct the study and develop the abstract.: Genesis Research Group. M. Kent: Financial Interests, Institutional, Funding, MK is employed by Genesis Research Group which received funds from Pfizer to conduct the study and develop the abstract.: Genesis Research Group. C. Tsang: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer; Non-Financial Interests, Personal and Institutional, Member of Board of Directors: GetReal Institute.