Abstract
The final overall survival (OS) results for the ADAURA trial show that osimertinib reduces the risk of death by 51% in patients with EGFR-mutated non–small cell lung cancer. For stage II or IIIA disease, the 5-year OS was 85% in patients who received osimertinib and 73% in the control group. The findings were nearly identical when patients with stage IB tumors were included in the analysis.
The anxiously awaited overall survival (OS) results for the ADAURA trial of osimertinib (Tagrisso; AstraZeneca) reveal that the drug boosts survival in patients with EGFR-mutated non–small cell lung cancer (NSCLC). Data presented at the 2023 American Society of Clinical Oncology Annual Meeting in Chicago, IL, and simultaneously published show that the drug reduced the risk of death by 51% (N Engl J Med 2023;389:137–47).
The phase III trial included 682 patients with stage IB, II, or IIIA EGFR-mutated NSCLC. Following surgery, half of the patients received osimertinib for up to 3 years; the rest received a placebo. In 2020, positive disease-free survival (DFS) results from the trial led the FDA to approve osimertinib as an adjuvant therapy for this indication (N Engl J Med 2020;383:1711–23).
Many oncologists began prescribing the drug because of the DFS benefit, but some held out for the OS findings, said Suresh Ramalingam, MD, of the Emory University School of Medicine in Atlanta, GA, who wasn't connected to the trial. “Doctors had to tell patients, ‘We don't know if it makes you live longer.’”
At the meeting, Roy Herbst, MD, PhD, of Yale School of Medicine in New Haven, CT, reported that the drug worked well for patients with stage II or IIIA tumors. The hazard ratio for the OS was 0.49, indicating that the treatment group had a 51% reduction in the risk of death. The 5-year OS in patients who received the drug was 85% compared with 73% in the control group. The disease recurred in 27% of patients treated with osimertinib and 60% of patients who received the placebo.
In a separate analysis, Herbst and colleagues included the patients with stage IB tumors. Again, osimertinib cut the risk of death by 51%. In the treatment group, 88% of patients were alive after 5 years versus 78% for the control group. The researchers had already reported the safety data, which indicated that 79% of patients in the osimertinib group developed side effects of grade 3 or above versus 48% of the patients in the control group. The most common side effects of osimertinib were diarrhea, nail infections, and dry skin.
The OS data are important “because some providers and even patients are on the fence” about using the drug, said David Spigel, MD, of the Sarah Cannon Research Institute in Nashville, TN, who wasn't connected to the research. But the improved OS results “are compelling across the board.” In addition, the findings emphasize the importance of EGFR testing before patients with NSCLC begin treatment, he said. It's recommended, but “it isn't always being done.”
Although the earlier DFS data suggested that the drug would be effective, Justin Gainor, MD, of Massachusetts General Hospital in Boston, who had no role in the trial, said that the results surprised him. “I was not expecting to see such a profound survival benefit.” Now, he says further research is necessary to determine whether “that impact on survival means we are curing more patients.”
Patients in the trial and in clinical practice take osimertinib for up to 3 years, noted Ramalingam. Because monitoring of patients will continue, the study will provide insight into how patients fare after that point and whether further treatment is necessary. –Mitch Leslie
For more news on cancer research, visit Cancer Discovery online at https://aacrjournals.org/CDNews.
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