Updated ADAURA Findings Favor Osimertinib Vs Placebo in NSCLC

Adjuvant osimertinib (Tagrisso) continued to prolong disease-free survival (DFS) and reduced the risk of disease recurrence better than placebo in patients with resected, EGFR-mutated non–small cell lung cancer (NSCLC), according to updated findings from the phase 3 ADAURA trial (NCT02511106) that were published in the Journal of Clinical Oncology.

Investigators of the phase 3 ADAURA trial stated that the updated data "demonstrate osimertinib to be a compelling therapeutic option to reduce the risk of developing [central nervous system] metastases in resected EGFR-mutated [non–small cell lung cancer.]"

Among patients with stage II to IIIA disease, the 4-year DFS rate in the osimertinib group was 70% (95% CI, 62%-76%) vs 29% (95% CI, 23%-35%) in the placebo group (HR 0.23; 95% CI, 0.18-0.30) after a median follow-up of 44.2 and 19.6 months, respectively. The corresponding DFS rates in the overall population were 73% (95% CI 67%-78%) and 38% (95% CI, 32%-43%) with osimertinib and placebo, respectively (HR 0.27; 95% CI, 0.21-0.34).

The osimertinib group also experienced fewer local or distant recurrences than the placebo group. The toxicity profile of osimertinib was consistent with the study’s primary analysis.

“The early separation in the Kaplan-Meier curves reported in the primary analysis was sustained to the last observed date in this updated analysis,” the investigators wrote. “There was an observed trend toward an increased DFS event rate beyond 36 months compared with the previous 36 months in the osimertinib group; however, the benefit of osimertinib treatment is clearly maintained as the curves remain separated beyond the 3-year treatment period.

“This observation suggests that some patients may benefit from adjuvant osimertinib beyond 3 years; molecular profiling and monitoring of minimal residual disease may help inform optimal treatment duration.”

A total of 682 patients enrolled on the international, double-blind ADAURA trial between November 2015 to February 2019. They were randomly assigned 1:1 to receive either osimertinib (n = 339) or placebo (n = 343). Most patients in the osimertinib and placebo groups, respectively, had malignant adenocarcinoma (54% and 55%), and roughly a quarter of all patients had acinar adenocarcinoma.

The median age was 64 years (range, 30-86) in the osimertinib group and 62 years (range, 31-82) in the placebo group. Most patients were women (68% and 72%) and Asian (64% and 64%). Patients received oral osimertinib or placebo at 80 mg once daily for up to 3 years, until disease recurrence, or meeting treatment discontinuation criterion.

Median DFS was 65.8 months (95% CI, 54.4-not calculable [NC]) in the osimertinib group vs 21.9 months (95% CI, 16.6-27.5) in the placebo group. Significantly more patients were alive and disease-free at 48 months in the osimertinib group (70%; 95% CI, 62%-76%) than in the placebo group (29%; 95% CI, 23%-35%).

The clinical benefit of osimertinib persisted across all predefined subgroups. Moreover, for patients with stage II-IIIA disease, the estimated probability of central nervous system (CNS) recurrence at 36 months was 2% (95% CI, 0.86%-5.03%) with osimertinib vs 13% (95% CI, 8.52%-18.48%) with placebo.

“These updated ADAURA data demonstrate osimertinib to be a compelling therapeutic option to reduce the risk of developing CNS metastases in resected EGFR-mutated NSCLC,” the investigators wrote.

Adverse effects (AEs) occurred in nearly all patients in both the osimertinib and placebo groups (98% and 90%). The incidence of grade 3 or higher AEs was 23% in the osimertinib group and 14% in the placebo group, and the incidence of AEs investigators thought were potentially related to treatment was 91% with osimertinib and 58% with placebo. Serious AEs affected 20% of those treated with osimertinib vs 14% with placebo.

The most common grade 1/2 AEs in the osimertinib arm and placebo arm, respectively, were diarrhea (47% vs 20%), paronychia (27% vs 1%), and dry skin (25% vs 7%). Interstitial lung disease occurred in 3% of patients in the osimertinib group vs 0% in the placebo group. Investigators recorded cardiac events in 6% and 3% of patients in the osimertinib and placebo groups, respectively.

“Future data of interest from ADAURA include long-term safety, subsequent treatment patterns, and overall survival. Tumor and circulating tumor DNA molecular profiling for analyses of minimal residual disease and acquired resistance may provide important information on persistence and resistance mechanisms to optimize treatment strategies in this setting,” the investigators concluded.

Reference

Herbst RS, Wu YL, John T, et al. Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: updated results from the phase III randomized ADAURA trial. J Clin Oncol. Published online January 31, 2023. doi:10.1200/JCO.22.02186