medwireNews: Extended follow-up data from the ADAURA trial show that the disease-free survival (DFS) benefit with adjuvant osimertinib over placebo continues beyond the 3-year treatment duration in people with EGFR-mutated stage IB–IIIA non-small-cell lung cancer (NSCLC).
Speaking at the ESMO Congress 2022 in Paris, France, Masahiro Tsuboi, from the National Cancer Center Hospital East in Kashiwa, Japan, said the “updated data reinforce adjuvant osimertinib as standard of care for [these patients] after complete tumor resection, with or without adjuvant chemotherapy.”
The primary analysis of the phase 3 trial showed that use of adjuvant osimertinib 80 mg once daily for up to 3 years was associated with a significant 83% reduced risk for disease recurrence or death among patients with stage II–IIIA disease (the primary endpoint) and an 80% reduction in those with stage IB–IIIA disease versus placebo.
In this updated analysis, with an additional 2 years of follow-up, median DFS was 65.8 months in the 233 participants with stage II–IIIA disease who received osimertinib and 21.9 months among the 237 who received placebo. Median follow-up duration was 44.2 and 19.6 months, respectively.
The difference between the two arms corresponded to a significant 77% lower risk for disease progression or death in favor of osimertinib. At 3 years, the DFS rate was 84% with osimertinib versus 34% with placebo, and at 4 years the rates were 70% and 29%, respectively.
Tsuboi said that the findings show that osimertinib “continued to demonstrate a clinically significant DFS benefit.”
A similar pattern was observed for central nervous system DFS in the primary study cohort (hazard ratio [HR]=0.24), and for overall DFS in the full study cohort (stage IB–IIIA; HR=0.27), with all outcomes, including those in subgroup analyses, favoring osimertinib.
The presenter also noted that no new safety concerns were reported during the extended follow-up period, which included a median 35.8 months of exposure to osimertinib.
Session discussant Sanjay Popat, from the Royal Marsden NHS Foundation Trust in London, UK, said that “the DFS impact remains strong and is clinically impactful.”
He continued: “Adjuvant osimertinib remains, albeit arguably, [an] important treatment option for our patients, despite no mature overall survival data.”
However, he pointed out that the survival curves appear to show the first signs of a possible tyrosine kinase inhibitor waning effect after treatment discontinuation in patients with stage II and IIIA disease. The effect was less obvious in patients with stage IA disease but Popat suggested this could be related to a lack of events.
He said: “Given this waning effect, the optimal osimertinib duration in stage II and IIIA disease is undefined.”
He added that it is unclear “whether osimertinib is simply delaying relapse and if extended adjuvant osimertinib (more than 3 years) dosing is actually needed versus treatment on relapse.” Moreover, “[t]he potential waning effect argues strongly for treatment with adjuvant chemotherapy when indicated.”
Popat concluded that he looks forward to additional data on longer term disease-free survival, patterns of relapse over time, outcomes by minimal residual disease, and overall survival.
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