Abstract 1165P
Background
∼30% of patients (pts) with NSCLC present with resectable disease. In the ADAURA trial (NCT02511106), there was a significant disease-free survival (DFS) benefit with osimertinib vs placebo (PBO) in pts with completely resected stg IB–IIIA EGFRm NSCLC (hazard ratio [HR] 0.20 [adjusted 99.12% CI 0.14, 0.30], p<0.001; 11% and 46% maturity for osimertinib and PBO, respectively); overall survival (OS) data were immature (29 pts died: osimertinib n=9/339, PBO n=20/343). Payers require estimates on survival benefits of novel oncology treatments to inform reimbursement decisions. We estimated long term OS following adjuvant osimertinib treatment in stg IB–IIIA EGFRm NSCLC.
Methods
A 5-state semi-Markov model, similar to those from other adjuvant oncology analyses and validated by clinical experts, was used to simulate the disease course of stg IB–IIIA EGFRm NSCLC over a lifetime horizon. Time to local/regional recurrence (LRR) and distant metastases (DM) from ADAURA were extrapolated separately using standard parametric modelling and analysed jointly using competing risks methodology. External sources (FLAURA [NCT02296125], meta-analyses, real-world evidence) informed the clinical pathway from LRR and DM. The PBO arm was modelled to receive osimertinib in the metastatic setting; the model assumed no osimertinib retreatment in the metastatic setting. Of pts predicted to be disease free after 5 yrs untreated (osimertinib arm: 3 yrs treatment + 5 yrs untreated; PBO arm: 5 yrs untreated) 95% were assumed ‘cured’ (experiencing non NSCLC mortality).
Results
The model predicted improved OS with osimertinib vs PBO in the adjuvant setting (Table). Table: 1165P
| Stage IB–IIIA EGFRm NSCLC | Median life-years OS (95% CI) | Patients alive at 10 years (95% CI) |
| Osimertinib | 11.42 (9.09, 14.66) | 54.9% (52.0, 57.6) |
| Placebo | 7.33 (6.76, 7.97) | 37.5% (34.0, 40.9) |
| Incremental life-years osimertinib vs placebo | 4.08 (1.53, 7.09) | - |
CI, confidence interval; Life-years, patient spends 1 month in each cycle; lifetime horizon, 63–100 years
Conclusions
Based on this model, adjuvant osimertinib is predicted to increase life expectancy vs PBO for stg IB–IIIA EGFRm NSCLC, with a substantial proportion of time spent disease free and a 17.4% absolute improvement in OS at 10 yrs. Mature data from ADAURA will inform long term survival outcomes.
Clinical trial identification
Editorial acknowledgement
Alexandra Webster, MSc, of Ashfield MedComms, for editorial support that was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
P.K. Cheema: Financial Interests, Personal, Invited Speaker, Honorarium: AstraZeneca; Financial Interests, Personal, Invited Speaker, Honorarium: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Honorarium: Merck; Financial Interests, Personal, Advisory Role, Honorarium: AstraZeneca; Financial Interests, Personal, Advisory Role, Honorarium: Amgen; Financial Interests, Personal, Advisory Role, Honorarium: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Honorarium: Novartis; Financial Interests, Personal, Advisory Role, Honorarium: Roche; Financial Interests, Personal, Advisory Role, Honorarium: Pfizer; Financial Interests, Personal, Advisory Role, Honorarium: EMD Serono; Financial Interests, Personal, Advisory Role, Honorarium: Merck. B. Heeg: Financial Interests, Personal, Full or part-time Employment, Ingress Health was contracted by AstraZeneca; Financial Interests, Institutional, Other: Ingress Health. Y. Wu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche. T. John: Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Bristol Myers Squibb; Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Funding: Takeda; Financial Interests, Personal, Funding: Boehringer Ingelheim; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: Ignyta; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: Bayer. F.A. Shepherd: Financial Interests, Personal, Stocks/Shares: AstraZeneca. F. de Marinis: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Role, Consultancy fees: Roche; Financial Interests, Personal, Advisory Role, Consultancy fees: BMS; Financial Interests, Personal, Advisory Role, Consultancy fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy fees: MSD. B. Samson: Financial Interests, Personal, Advisory Board, Honorarium: AstraZeneca. S. Shaw: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca. M. Miranda: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Verhoek: Financial Interests, Personal, Advisory Role, Consultancy fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy fees: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consultancy fees: Johnson & Johnson; Financial Interests, Personal, Advisory Role, Consultancy fees: Sanofi; Financial Interests, Personal, Advisory Role, Consultancy fees: Pfizer; Financial Interests, Personal, Advisory Role, Consultancy fees: Amgen; Financial Interests, Personal, Advisory Role, Consultancy fees: Eisai. All other authors have declared no conflicts of interest.