KEY TAKEAWAYS
- The phase III ADAURA trial (NCT02511106) showed that adjuvant osimertinib provides a significant DFS benefit in EGFR-mutated stage IB-IIIA NSCLC.
- ADURA Results Update: Osimertinib maintained extended DFS benefit over placebo, reduced local/distant recurrence risk, and improved CNS DFS in resected EGFR-mutated NSCLC
- 682 stage IB-IIIA EGFR-mutated NSCLC patients were randomized in the trial to receive osimertinib 80mg once-daily or placebo for 3 years. The primary endpoint was DFS by investigator assessment in stage II-IIIA disease analyzed by stratified log-rank test.
- The secondary endpoints included DFS in stage IB-IIIA, overall survival, and safety, and the recurrence patterns and CNS DFS were prespecified exploratory endpoints.
- Long-term safety profile of osimertinib consistent with primary analysis, updated data supports its efficacy in resected EGFR-mutated NSCLC adjuvant therapy.
Complete tumor excision in patients with EGFR-mutated stage IB-IIIA NSCLC showed a statistically significant improvement in disease-free survival (DFS) with adjuvant osimertinib compared to placebo (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30]; P<.001). They provide the results of a revised exploratory analysis of completed DFS data. 682 patients with EGFR-mutated (exon 19 deletion/L858R) NSCLC were randomly assigned 1:1 (stratified by stage, mutational status, and race) to receive osimertinib 80 mg once-daily or placebo for 3 years.
Patients were classified as having stage IB-IIIA disease according to the American Joint Committee on Cancer/Union for International Cancer Control, seventh edition. Investigator-assessed DFS in stage II-IIIA illness was the primary endpoint, and the stratified log-rank test was used to evaluate the data; once statistical significance in DFS was reported, further formal statistical testing was not intended. Overall survival, safety, and progression-free survival were secondary end goals. CNS disease-free survival and recurrence patterns were established as exploratory end objectives.
At the time of analysis (April 11, 2022), the median follow-up for patients with stage II-IIIA disease who received osimertinib was 44.2 months, while those who received a placebo had a much shorter 19.6 months; the disease-free survival HR for osimertinib was 0.23 (95% CI, 0.18 to 0.30), and the disease-free survival rate at 4 years was 70% for osimertinib and 29% for placebo (placebo). The 4-year DFS rate was 73% (osimertinib) and 38% (chemotherapy). The DFS HR was 0.27 (95% CI, 0.21 to 0.34).
Compared to the placebo, treatment with osimertinib reduced the number of patients who experienced both local and distant recurrence. The HR for CNS DFS in stage II-IIIA was 0.24 (95% CI: 0.14-0.42). In addition, consistent with the initial analysis, osimertinib’s long-term safety profile was evaluated. The efficacy of adjuvant osimertinib in resected EGFR-mutated NSCLC is supported by these revised results, which show a sustained DFS benefit over placebo, lower risk of local and distant recurrence, enhanced CNS DFS, and a consistent safety profile.
Source: https://pubmed.ncbi.nlm.nih.gov/36720083/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02511106
Herbst, R, Wu, YL, John, T., Grohe, C., Majem, M., Wang, J., Kato, T., Goldman, J, Laktionov, K., Kim, SW., Yu, CJ., Vu, H., Lu, S., Lee, K.Y., Mukhametshina, G., Akewanlop, C., Marinis F., Bonanno, L., Domine, M. and Shepherd, F.A., Urban D, Huang X, Bolanos A, Stachowiak M, Tsuboi M (2023). Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. Journal of Clinical Oncology. doi:https://doi.org/10.1200/jco.22.02186.
