Abstract 1201P
Background
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. Table: 1201P
| N ALC, N CRZ ALC vs CRZ HR 95% CI | PFS* | OS | |||||
| RWD† | ALEX-like RWD† | ALEX | RWD† | ALEX-like RWD† | ALEX | ||
| All patients | 141, 221 0.46 0.33–0.65 | 120, 203 0.46 0.32–0.66 | 152, 151 0.43 0.32–0.58 | 141, 223 0.46 0.31–0.69 | 120, 205 0.47 0.32–0.73 | 152, 151 0.70 0.48–1.02 | |
| Patients with baseline brain scans | Baseline CNS mets | 50, 50 0.27 0.14–0.53 | 44, 45 0.30 0.16–0.57 | 64, 58 0.37 0.23–0.58 | 50, 51 0.44 0.21–0.92 | 44, 46 0.41 0.20–0.83 | 64, 58 0.58 0.34–1.00 |
| No baseline CNS mets | 52, 90 0.35 0.20–0.62 | 45, 87 0.34 0.22–0.52 | 88, 93 0.46 0.31–0.68 | 52, 90 0.57 0.29–1.12 | 45, 87 0.53 0.25–1.14 | 88, 93 0.76 0.45–1.26 |
*Progression was not assessed in all patients in the electronic health record database †wHR
Clinical trial identification
NCT02075840.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Ben Castle, MSc, of Ashfield MedComms, an Ashfield Health company, and funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Funding
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Disclosure
M.G. Krebs: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: OM Pharma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Other, Travel expenses: BerGenBio; Financial Interests, Personal, Other, Travel expenses: Immutep; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BerGenBio; Financial Interests, Personal, Advisory Board: Achilles Therapeutics; Financial Interests, Institutional, Principal Investigator: Carrick; Financial Interests, Institutional, Principal Investigator: Turning Point Therapeutics; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Blueprint; Financial Interests, Institutional, Principal Investigator: BerGenBio; Financial Interests, Institutional, Principal Investigator: Immutep; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Seattle Genetics. J.J. Lin: Financial Interests, Personal, Advisory Role, Consultant: Genentech, Inc.; Financial Interests, Personal, Advisory Role, Consultant: C4 Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Role, Consultant: Nuvalent; Financial Interests, Personal, Advisory Role, Consultant: Turning Point Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Elevation Oncology; Financial Interests, Personal, Research Grant, Honorarium and travel support: Pfizer; Financial Interests, Institutional, Research Grant, Honorarium and travel support: Hengrui Therapeutics; Financial Interests, Institutional, Research Grant: Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: Neon Therapeutics; Financial Interests, Institutional, Research Grant: Relay Therapeutics; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Elevation Oncology; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Other, CME Funding: OncLive; Financial Interests, Personal, Other, CME Funding: MedStar Health; Financial Interests, Personal, Other, CME Funding: Northwell Health. N. Pal: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech; Financial Interests, Personal, Stocks/Shares: Roche/Genentech. L. Polito: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. H.T.L. Trinh: Financial Interests, Personal, Other, Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: Genentech, Inc. M.M.S.M. Hilton: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. V. Smoljanovic: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. N. Kurtsikidze: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. V. Archer: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. Q. Zhang: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc. Roche; Financial Interests, Personal, Stocks/Shares: Roche; Financial Interests, Personal, Stocks/Shares: Regeneron; Financial Interests, Personal, Stocks/Shares: BMS; Financial Interests, Personal, Stocks/Shares: AbbVie; Financial Interests, Personal, Stocks/Shares: AC Immune.