Abstract 1005P
Background
Aumolertinib (aumo), a third-generation (3rd gen) EGFR inhibitor (EGFRi), is being developed as a first-line treatment (1L tx) for patients with advanced EGFR mutation-positive (EGFR+) NSCLC. Osimertinib (osi) is a widely used 3rd gen EGFRi for 1L tx of EGFR+ NSCLC. Although both aumo and osi have demonstrated superior safety and efficacy to earlier generation EGFRis in clinical trials, no direct comparison of efficacy and safety has been done. The objective of this analysis was to compare progression-free survival (PFS), overall survival (OS), and any-grade treatment-emergent adverse events (AG-TEAE) for aumo vs osi utilizing an anchored indirect treatment comparison (ITC).
Methods
Two well-accepted ITC methods were used: a Bucher ITC , based on published aggregate data from the AENEAS (aumo) and FLAURA (osi) trials, and a simulated treatment comparison (STC) , using patient-level data from AENEAS and published aggregated data from FLAURA. In the STC, patients in AENEAS were regression-adjusted using the relationship between population characteristics and outcomes in AENEAS to predict the expected outcomes in the FLAURA trial population. Regression models were adjusted for identified potential effect modifiers and prognostic factors that were imbalanced across trials.
Results
For PFS, the primary efficacy endpoint, the Bucher ITC hazard ratio (HR) for aumo vs osi was 1.00 (95% CI: 0.72 - 1.39), and the STC HR was 0.98 (95% CI: 0.68 - 1.42), suggesting no difference. For OS, the Bucher HR suggests no statistical difference between aumo and osi (1.02 [95% CI: 0.67 - 1.56]), while the STC HR shows a numerical difference favoring aumo (0.73 [95% CI 0.44 - 1.22]). However, OS results from the AENEAS trial were not mature at the time of this analysis. For AG-TEAE, the Bucher ITC odds ratio for aumo vs osi was 0.65 (95% CI: 0.08 - 5.50). An STC was not conducted for AG-TEAE as variation across treatment groups was minimal.
Conclusions
For PFS, OS, and AG-TEAE, no statistical difference was detected between aumo and osi in either ITC method. These analyses provide a comparative assessment of aumo and osi in the absence of direct comparison data from the same trial.
Clinical trial identification
AENEAS: NCT03849768; FLAURA: NCT02296125.
Editorial acknowledgement
All authors provided editorial assistance in addition to: Rina Mehta, EQRx Rachel Cunningham, EQRx Beth Sawchyn, EQRx Brett Maiese, EQRx.
Legal entity responsible for the study
EQRx International, Inc.
Funding
EQRx International, Inc.
Disclosure
S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, BeiGene, Takeda, Lilly, Seattle Genetics, Turning Point Therapeutics, Xcovery, GlaxoSmithKline, MSD, Pfizer, Sanofi; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Touch Medical; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Ariad, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Trizel, GlaxoSmithKline, Takeda, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint, Seattle Genetics; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, , Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Invited Speaker, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. S. Stergiopoulos: Financial Interests, Institutional, Full or part-time Employment: EQRx; Financial Interests, Personal, Stocks/Shares: Roche. S. King: Financial Interests, Institutional, Full or part-time Employment: EQRx. M. Curtis: Financial Interests, Institutional, Full or part-time Employment: EQRx; Financial Interests, Institutional, Stocks/Shares: Roche. A. Dillon: Financial Interests, Institutional, Advisory Role: EQRx. R. Akehurst: Financial Interests, Institutional, Full or part-time Employment: Lumanity; Financial Interests, Institutional, Funding: EQRx. D. Lee: Financial Interests, Institutional, Full or part-time Employment: Lumanity; Financial Interests, Institutional, Funding: EQRx. F. Guelfucci: Financial Interests, Institutional, Full or part-time Employment: Syneos Health; Financial Interests, Institutional, Funding: EQrx. A. Ngami: Financial Interests, Institutional, Full or part-time Employment: Syneos Health; Financial Interests, Institutional, Funding: EQRx. F. Bianic: Financial Interests, Institutional, Full or part-time Employment: Syneos Health; Financial Interests, Institutional, Funding: EQRx. Y. Li: Financial Interests, Institutional, Full or part-time Employment: EQRx. S.M. Ali: Financial Interests, Institutional, Full or part-time Employment: EQRx; Financial Interests, Institutional, Advisory Role: In8bio, Pillar Biosciences, Droplet Biosciences; Financial Interests, Institutional, Sponsor/Funding: Elevation Oncology. V. Miller: Financial Interests, Institutional, Full or part-time Employment: EQRx; Financial Interests, Institutional, Stocks/Shares: Revolution Medicines, Mirati Therapeutics; Financial Interests, Institutional, Royalties: Sloan Kettering Institute for Cancer Research.