As reported in The New England Journal of Medicine by Wu et al, the phase III ADAURA trial has shown significantly prolonged disease-free survival with adjuvant osimertinib vs placebo in patients with resected EGFR-mutant non–small cell lung cancer (NSCLC). These findings were also presented during the Presidential Symposium at the ESMO Virtual Congress 2020 (Abstract LBA1).

Study Details

In the international double-blind trial, 682 patients with completely resected stage IB to IIIA disease were randomly assigned between November 2015 and February 2019 to receive osimertinib at 80 mg once daily (n = 339) or placebo (n = 343) for 3 years. Disease stage was IB in 212 patients (32% of each group), stage II in 236 (34% of each group), and stage IIIA in 234 (35% vs 34%). Overall, 60% of patients in each group received adjuvant chemotherapy. The primary endpoint was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary endpoints included disease-free survival in the overall population of patients with stage IB to IIIA disease and overall survival.

Disease-Free Survival

At 24 months, disease-free survival rates among patients with stage II to IIIA disease were 90% (95% confidence interval [CI] = 84%–93%) in the osimertinib group vs 44% (95% CI = 37%–51%) in the placebo group (hazard ratio [HR] = 0.17, 99.06% CI = 0.11–0.26, P < .001). Median disease-free survival was not reached (95% CI = 38.8 months–not estimable) in the osimertinib group vs 19.6 months (95% CI = 16.6–24.5 months) in the placebo group.

At 24 months, disease-free survival rates in the overall population were 89% (95% CI = 85%–92%) in the osimertinib group vs 52% (95% CI = 46%–58%) in the placebo group (HR = 0.20, 99.12% CI = 0.14–0.30, P < .001). Median disease-free survival was not reached (95% CI = not estimable–not estimable) in the osimertinib group vs 27.5 months (95% CI = 22.0–35.0 months) in the placebo group.

The disease-free survival benefit of osimertinib was consistent across all predefined subgroups, including disease stages IB (HR = 0.39, 95% CI = 0.18–0.76), II (HR = 0.17, 95% CI = 0.08–0.31), and IIIA (HR = 0.12, 95% CI = 0.07–0.20); and use (HR = 0.16, 95% CI = 0.10–0.26) and no use (HR = 0.23, 95% CI = 0.13­–0.40) of adjuvant chemotherapy.

At 24 months, 98% (95% CI = 95%–99%) of patients in the osimertinib group vs 85% (95% CI = 80%–89%) of patients in the placebo group were alive without central nervous system (CNS)-related disease (HR for CNS disease recurrence or death = 0.18, 95% CI = 0.10–0.33).

Overall survival data were immature at time of analysis. As of data cutoff, death had occurred in 9 patients in the osimertinib group and 20 in the placebo group.

Adverse Events

The most common adverse events of any grade in the osimertinib group were diarrhea (46% vs 20% in placebo group), paronychia (25% vs 1%), and dry skin (23% vs 6%). Grade ≥ 3 adverse events occurred in 20% of patients in the osimertinib group and 13% of patients in the placebo group. Serious adverse events were reported in 16% vs 12% of patients. Adverse events led to discontinuation of treatment in 11% vs 3%. No fatal adverse events were reported in the osimertinib group; one fatal adverse event (pulmonary embolism) occurred in the placebo group.

The investigators concluded, “In patients with stage IB to IIIA EGFR mutation–positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo.”

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit nejm.org.