medwireNews: Adjuvant treatment with osimertinib significantly prolongs overall survival (OS) relative to placebo in people with EGFR-mutated, early-stage non-small-cell lung cancer (NSCLC), show trial results presented at the 2023 ASCO Annual Meeting.
Speaking to the press in Chicago, Illinois, USA, study author Roy Herbst (Yale Cancer Center, New Haven, Connecticut, USA) said: “Together with the practice-changing disease-free survival data from our primary analysis, the overall survival benefit instills confidence that adjuvant osimertinib is the standard of care for patients with resected EGFR-[mutated] stage IB–IIIA non-small-cell lung cancer.
“This further reinforces the need to identify these patients with available biomarkers at the time of diagnosis and before treatment begins.”
In the phase 3 ADAURA trial, 682 individuals with completely resected, stage IB–IIIA NSCLC and either the EGFR exon 19 deletion (55%) or exon 21 L858R mutation (45%) were randomly assigned to receive adjuvant osimertinib 80 mg/day or placebo for up to 3 years. The majority of participants were women – 68% in the osimertinib group and 72% in the placebo group – and an identical 64% in each group were Asian, while 60% had received adjuvant chemotherapy.
As reported by Herbst, in the primary efficacy population comprising patients with stage II or IIIA disease, the 5-year OS rate was 85% for those who received osimertinib and 73% for those given placebo. This equated to a significant 51% reduced risk for death with the third-generation EGFR–tyrosine kinase inhibitor.
Osimertinib also significantly improved OS versus placebo in the overall population of patients with stage IB–IIIA disease, with 5-year rates of 88% and 78%, respectively, and an identical 51% reduction in the risk for death.
An exploratory analysis of OS in predefined subgroups demonstrated “a consistent benefit” of osimertinib across all patient subgroups, including by disease stage, EGFR mutation type, and prior adjuvant chemotherapy use, “with impressive hazard ratios ranging from 0.33 to 0.68,” reported the presenter.
He added that safety findings with extended follow-up were previously published and “were consistent with the ADAURA primary analysis and established profile of osimertinib.”
Herbst noted that at the time of data cutoff for the OS analysis, just one additional serious adverse event within 28 days of treatment discontinuation had been reported – a case of COVID-19 pneumonia that was not considered related to osimertinib.
The presenter concluded that the “disease-free survival benefit in ADAURA has translated into a statistically significant overall survival benefit with osimertinib,” making the agent the first targeted therapy to demonstrate an OS advantage in this setting.
Speaking to the future, he highlighted that extended follow-up for OS in the trial is ongoing, as are translational analyses, including tumor and circulating tumor DNA molecular profiling of minimal residual disease with an aim to “provide more information on persistence and resistance mechanisms.”
Discussant Benjamin Solomon (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) described the results as “groundbreaking” and said: “These unprecedented overall survival results in early-stage NSCLC are practice changing or practice affirming (for those who had already changed practice).”
He believes “they dispel the notion of equivalence between early treatment with osimertinib and treatment on recurrence.”
Solomon congratulated the ADAURA investigators for a trial “that moves targeted therapies from advanced disease to the early-stage setting and opens up a new chapter for precision medicine with targeted therapy in early-stage non-small-cell lung cancer.”
The discussant pointed out, however, that several questions need to be addressed, such as defining the optimal duration of osimertinib therapy, identifying the patients who will benefit, and determining the options after relapse.
The ADAURA OS results are simultaneously published in The New England Journal of Medicine.
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2023 ASCO Annual Meeting; Chicago, Illinois, USA: 2–6 June
N Engl J Med 2023; doi:10.1056/NEJMoa2304594