Osimertinib in the adjuvant treatment setting significantly improves disease-free survival (DFS) in patients with localized non–small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation.
In the ADAURA phase 3 multinational trial, 90% of patients with stage II-IIIA NSCLC who received osimertinib were alive at 2 years without recurrence, compared with 44% who received placebo. There was an 83% reduction in the risk of disease recurrence or death in patients with stage II-IIIA disease who were treated with adjuvant osimertinib versus placebo, said Roy S. Herbst, MD, PhD, at the ASCO20 Virtual Scientific Program.
Rates of disease recurrence or death following surgery and adjuvant chemotherapy for NSCLC remain high, with the 5-year overall survival benefit of only 5% in patients with early-stage NSCLC. By disease stage, 5-year recurrence rates are 45% in stage IB, 62% in stage II, and 76% in stage III. These high recurrence rates signal an unmet need in this population.
“Adjuvant osimertinib is the first targeted agent in a global randomized trial to show a statistically significant and clinically meaningful improvement in DFS in patients with stage IB/II/IIIA EGFR mutation–positive NSCLC,” said Dr Herbst, chief of medical oncology at Yale Cancer Center, New Haven, CT. “Adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB/II/III EGFR mutation–positive NSCLC after complete tumor resection.”
ADAURA randomized 682 patients with primary nonsquamous stage IB-IIIA NSCLC and confirmed EGFR mutation to receive osimertinib 80 mg once daily or placebo until disease recurrence, with planned treatment for 3 years. Eligible participants had complete resection of primary NSCLC with negative margins, with or without adjuvant chemotherapy.
Baseline patient characteristics were balanced across the 2 arms. Thirty-one percent of patients in both groups had stage IB disease and 69% had stage II/IIIA disease. More patients in both arms were female—68% and 72% in the osimertinib and placebo groups, respectively.
The Independent Data Monitoring Committee had a planned meeting in April 2020, and “the results looked so good that they decided that the trial needed to be unblinded,” said Dr Herbst. “If I was on the Committee, I would have done the same thing. These are extraordinary results.” At the time of unblinding, the study had completed enrollment and all patients were followed for at least 1 year.
In the patients with stage IIA-IIIA disease, median DFS was not reached in the osimertinib arm versus 20.4 months in the placebo arm, corresponding to the 83% reduction in risk in the osimertinib arm (P <.0001).
In the overall study population, which included patients with stage IB disease, the risk of disease recurrence was reduced by 79% in the osimertinib arm compared with placebo, with a median DFS not reached in the osimertinib group compared with a median DFS of 28.1 months in the placebo group (P <.0001).
In every prespecified subgroup, including by disease stage, receipt of adjuvant chemotherapy, and EGFR mutation status (exon 19 deletions or exon 21 L858R mutations), the results favored osimertinib in terms of DFS, said Dr Herbst. Overall survival, a secondary end point, was immature at the time of data analysis.
The median duration of exposure to osimertinib was 22 months. The safety profile in this study was consistent with the known safety profile of osimertinib, and the drug was generally tolerable. Interstitial lung disease was reported in 3% of the osimertinib group, and QTc prolongation was reported in 7% of the osimertinib group versus 1% of the placebo group.
“This trial is a home run,” said Dr Herbst. “It’s an important advance to see a targeted therapy significantly delay disease recurrence following surgery in patients with NSCLC. We can now treat patients earlier.”
“The improvement in DFS seen in this study strongly supports the use of this targeted therapy in earlier-stage disease, which has a significant risk of recurrence despite surgical treatment and chemotherapy,” commented ASCO Chief Medical Officer and Executive Vice President Richard L. Schilsky, MD.