Abstract 25P
Background
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.
Methods
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.
Results
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: 25P
| Second-line treatment | Patients, n | Median OS (95% CI), months |
| Overall (all pts receiving 2L therapy) | 299 | 13.2 (11.8, 16.0) |
| EGFR-TKIs (1st/2nd/3rd generation) | 49 | 19.9 (14.8, 28.8) |
| - Osi | 15 | 20.9 (12.3, NC) |
| CTx alone | 44 | 9.8 (7.4, 18.3) |
| Clinical study drug | 25 | 16.0 (13.0, NC) |
| Any IO (monotherapy or +CTx) | 103 | 10.8 (7.4, 13.3) |
| - IO alone | 28 | 3.2 (2.1, 8.9) |
| - IO + CTx | 75 | 12.5 (10.8, 17.0) |
| Osi combination therapy | 78 | 15.8 (11.7, 21.8) |
| - Osi + CTx | 46 | 11.7 (9.6, 18.7) |
| - Osi + other* | 32 | 21.8 (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.
Conclusions
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.
Editorial acknowledgement
Medical writing support was provided by Hedley Coppock, Ph.D., of Ashfield MedComms, an Inizio company, for medical writing support that was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
F. Griesinger: Financial Interests, Institutional, Research Grant: ASTRA, Boehringer Ingelheim, BMS, Lilly, Novartis, Roche, MSD, Pfizer, Takeda, Siemens, Amgen, GSKD, Sanofi; Financial Interests, Personal, Other, Consulting fees; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Support for attending meetings and/or travel; Participation on a Data Safety Monitoring Board or Advisory Board: ASTRA; Financial Interests, Personal, Other: Boehringer Ingelheim, BMS, Lilly, Novartis, Roche, MSD, Pfizer, Takeda, Siemens, Amgen, GSK, Sanofi, Daiichi Sankyo, BeiGene. D. Shah: Financial Interests, Institutional, Funding: ANTHOS Inc, Guardant, AstraZeneca. R.J. Salomonsen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. J. Chapaneri: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Cooper: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. P.S. Karia: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Royalties: UpToDate. J.J. Nieva: Financial Interests, Personal, Invited Speaker: Genentech; Financial Interests, Personal, Writing Engagements: AstraZeneca; Financial Interests, Personal, Ownership Interest: Cansera; Financial Interests, Personal, Stocks/Shares: Amgen, Johnson & Johnson, Novartis; Financial Interests, Personal, Research Grant: Merck, Genentech; Financial Interests, Personal, Advisory Role: ANP Technologies, Aadi Biosciences, BioAtla, G1 Therapeutics, Mindmed, Naveris, Kalivir.