25P Real-world treatment patterns and outcomes in the US after first-line (1L) osimertinib (osi) in patients with epidermal growth factor receptor (EGFR)-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC)

Osi is a third-generation, central nervous system (CNS)-active, oral EGFR-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits EGFR-TKI sensitising and EGFR T790M resistance mutations. It is the preferred 1L therapy for EGFRm advanced NSCLC. However, patients (pts) may progress after 1L osi and need subsequent therapy. Real-world second-line (2L) therapy data in this population are lacking. Hence, we characterised 2L treatment patterns and outcomes after 1L osi in a US cohort. Pts with EGFRm advanced NSCLC treated with 1L osi from 2018–2020 were identified from the Flatiron Health Database. Line of therapy was considered new if there was a gap of >120 days between sequential drug episodes. 2L therapies were described and overall survival (OS) was summarised by 2L therapy. In total, 773 pts were assessed. At data cut-off (Jan 2023; median overall follow-up: 24 months; median follow-up for pts with subsequent therapy: 29 months), of the 773 assessable pts, 299 (39%) received 2L therapy, 173 (22%) remained on 1L osi, 251 (32%) had died with no subsequent therapy and 50 (7%) were alive with no subsequent therapy. The most common 2L therapy was osi combination therapy (26%), followed by immunotherapy (IO) + chemotherapy (CTx) (25%), EGFR-TKIs alone (16%), CTx alone (15%), IO alone (9%), and clinical study drug (8%). Most pts receiving osi combinations received osi + CTx (59%). Median OS (95% confidence interval [CI]) following 2L treatment is shown in the table. There was substantial variation in 2L treatment patterns by CNS metastasis at baseline and EGFR mutation subtype; these data will be presented.Table: 25PSecond-line treatmentPatients, nMedian OS (95% CI), monthsOverall (all pts receiving 2L therapy)29913.2 (11.8, 16.0)EGFR-TKIs (1st/2nd/3rd generation)4919.9 (14.8, 28.8)- Osi1520.9 (12.3, NC)CTx alone449.8 (7.4, 18.3)Clinical study drug2516.0 (13.0, NC)Any IO (monotherapy or +CTx)10310.8 (7.4, 13.3)- IO alone283.2 (2.1, 8.9)- IO + CTx7512.5 (10.8, 17.0)Osi combination therapy7815.8 (11.7, 21.8)- Osi + CTx4611.7 (9.6, 18.7)- Osi + other*3221.8 (14.5, NC)*Includes IO + CTx (19/32; 59%), clinical study drug (4/32; 13%), 1st/2nd generation EGFR-TKIs (4/32; 12.5%), hormones (3/32; 9%), and IO (2/32; 6%). NC, non-calculable. Open table in a new tab *Includes IO + CTx (19/32; 59%), clinical study drug (4/32; 13%), 1st/2nd generation EGFR-TKIs (4/32; 12.5%), hormones (3/32; 9%), and IO (2/32; 6%). NC, non-calculable. Over a third of pts received no 2L therapy after 1L osi. The most frequent 2L therapies were osi combination therapy and IO + CTx. Our results emphasise that pts should receive the most effective therapy in the 1L setting. OS by 2L therapy.