Real-world comparative effectiveness of 1L alectinib (ALC) vs crizotinib (CRZ) in patients (pts) with ALK plus advanced NSCLC with or without baseline CNS metastases (mets)
AuthorsKrebs, Matthew G
Lin, J. J.
Trinh, H. L.
AffiliationDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
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AbstractBackground The phase III ALEX study (NCT02075840) demonstrated superiority of ALC vs CRZ for treatment of advanced ALK+ NSCLC. In this study, real-world comparative effectiveness of 1L ALC vs CRZ was retrospectively analysed. Methods Adult pts with advanced ALK+ NSCLC who received 1L ALC (from 11 Dec 2015) or CRZ (from 1 Jan 2014) were included from the nationwide Flatiron Health electronic health record-derived de-identified database. Propensity scores were applied to balance baseline characteristics. Weighted hazard ratios (wHR) of ALC vs CRZ were calculated for real-world outcomes, including progression-free survival (rwPFS), overall survival (rwOS) and time to first/new CNS met (rwTTNCM; death was included as an event). In pts with baseline brain scans, outcomes in pts with or without baseline CNS mets were analyzed. Sensitivity analyses were performed in pts with known ECOG PS or treated after 11 Dec 2015. To compare real-world comparative effectiveness with the ALEX study, a population filtered by ALEX laboratory inclusion/exclusion criteria (ALEX-like RWD cohort) was analysed, and wHRs compared with corresponding HRs from ALEX. Results The RWD cohort comprised 364 pts (141 ALC; 223 CRZ); differences in baseline characteristics were: CNS mets (38 vs 26%), Asian race (15 vs 5%), known PD-L1 status (72 vs 15%) and known ECOG PS (65 vs 48%). In the RWD cohort, rwPFS and rwOS were significantly improved with ALC vs CRZ (Table). In 243 pts with baseline brain scans (102 ALC; 141 CRZ), a significant rwPFS benefit was seen regardless of baseline CNS mets. In pts without baseline CNS mets, development of first CNS met was delayed with ALC vs CRZ (rwTTNCM: adjusted HR=0.42, 95% CI 0.24�0.77). The ALEX-like RWD cohort comprised 325 pts (120 ALC; 205 CRZ); wHRs of ALC vs CRZ for rwPFS showed similar benefit to ALEX (Table). Conclusions Outcomes were significantly improved with 1L ALC vs CRZ in pts with advanced ALK+ NSCLC in the real-world setting.
CitationKrebs MG, Lin JJ, Pal N, Polito L, Trinh HTL, Hilton MMSM, et al. 1201P Real-world comparative effectiveness of 1L alectinib (ALC) vs crizotinib (CRZ) in patients (pts) with ALK+ advanced NSCLC with or without baseline CNS metastases (mets). Vol. 32, Annals of Oncology. Elsevier BV; 2021. p. S959.
JournalAnnals of Oncology