Treatment with osimertinib (Tagrisso) in the adjuvant setting significantly improves disease-free survival (DFS) in patients with localized non–small-cell lung cancer (NSCLC) with an EGFR mutation, according to results presented by Roy S. Herbst, MD, PhD, FACP, FASCO, Chief of Medical Oncology, Yale Cancer Center, New Haven, CT, at the ASCO 2020 virtual annual meeting.
In the phase 3 multinational ADAURA clinical trial, 90% of patients with stage II to stage IIIA NSCLC who received osimertinib were alive at 2 years without disease recurrence, compared with 44% who received placebo. Furthermore, an 83% reduction in the risk for disease recurrence or death was seen in patients who received adjuvant osimertinib treatment compared with placebo.
The rates of disease recurrence or death after surgery and adjuvant chemotherapy for NSCLC remain high, with a 5-year overall survival (OS) benefit of only 5% in patients with early-stage NSCLC. By disease stage, the 5-year recurrence rates in patients with NSCLC are 45% in stage IB, 62% in stage II, and 76% in stage III. These high recurrence rates signal an unmet need in this patient 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. “Adjuvant osimertinib provides a highly effective, practice-changing treatment for patients with stage IB/II/III EGFR mutation–positive NSCLC after complete tumor resection.”
A total of 682 patients with primary nonsquamous stage IB to IIIA NSCLC and confirmed EGFR mutation were randomized to osimertinib 80 mg once daily or to placebo until disease recurrence, with a planned treatment for 3 years. Eligible patients had complete resection of the primary NSCLC with negative margins, with or without adjuvant chemotherapy.
The baseline patient characteristics were balanced across the 2 study arms. Of all the patients, 31% had stage IB disease and 69% had stage II/IIIA disease. More patients in both arms were female (68% in the osimertinib group and 72% in the placebo group).
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,” Dr Herbst said. “If I were 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 to IIIA disease, the median DFS was not reached in the osimertinib arm versus 20.4 months in the placebo arm, corresponding to an 83% risk reduction with osimertinib versus placebo (P <.0001).
In the overall study population, which also included patients with stage IB disease, the risk for disease recurrence was reduced by 79% in the osimertinib arm versus placebo, with a median DFS not reached in the osimertinib group and 28.1 months in the placebo group (P <.0001).
In every prespecified subgroup, including by disease stage, receipt of adjuvant chemotherapy, and the presence of an EGFR mutation (exon 19 deletions or exon 21 L858R mutations), the results favored osimertinib in terms of DFS, said Dr Herbst. OS, 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 patients receiving osimertinib, and corrected QT 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.”
ASCO Chief Medical Officer and Executive Vice President Richard L. Schilsky, MD, FACP, FSCT, FASCO, commented on this study. “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,” Dr Schilsky said.