A new analysis of ADAURA data shows osimertinib cuts the risk of brain metastases or death by 82% compared with placebo in certain early-stage patients with NSCLC.
Patients treated with osimertinib after surgery for early-stage EGFR-mutated non-small cell lung cancer (NSCLC) were far less likely to see their cancer later reappear in the brain, which often happens with this type of disease.
The findings, presented today during the European Society of Medical Oncology (ESMO) Virtual Congress 2020, report exploratory results from the phase 3 ADAURA trial, which previously found that osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), should become the treatment of choice for patients with the mutation once they receive surgery for early-stage, localized NSCLC.
The therapy, marketed by AstraZeneca as Tagrisso, is already approved to treat patients with advanced EGFR-mutated NSCLC. In July, FDA granted breakthrough therapy status for osimertinib in this early stage indication, after the ADAURA trial was stopped early in April due to overwhelming efficacy. Initial results presented at the American Society of Clinical Oncology (ASCO) showed the treatment reduced risk of disease recurrence or death by 79% compared with placebo.
These latest results, which appeared simultaneously in the New England Journal of Medicine, involve 682 patients randomized to osimertinib (339 patients) or placebo (343 patients). At 24 months, 90% of those with stage II to stage IIIA disease taking the study drug were alive and disease-free (HR 0.17, 99.06% CI, 0.11-0.26, P < .001). Overall, 89% of those taking osimertinib compared with 52% in the placebo group were alive and disease-free at 24 months; the overall HR for disease recurrence or death was 0.20 (99.12% CI, 0.14-0.30, P < .001).
At ASCO, investigators said that for 30% of patients with NSCLC, the cancer is caught early enough for surgery to make them cancer-free, the disease often reappears elsewhere in the body, and patients who have central nervous system (CNS) or brain metastases have a particularly grim outlook.
The most striking finding presented today was the dramatic drop in the likelihood of brain metastases: patients taking the study drug saw an 82% reduction in the risk of cancer recurrence in the central nervous system (brain cancer) or death; hazard ratio (HR) was 0.18 (CI 95%, 0.10-0.33, P < .0001). Investigators reported that the median disease-free survival for CNS cancer had not been reached in either arm by the time of data cut-off.
Investigators estimate that for patients who did not have another type of cancer recurrence, the probability of this type of lung cancer metastasizing to the brain 18 months was less than 1% for patients who took osimertinib alongside usual care, compared with 9% for patients treated with placebo and usual care. One of the landmark findings in ADAURA presented at ASCO was that even among patients who had not received chemotherapy, median DFS for osimertinib was not reached, compared with 33.1 months for those taking placebo.
“It’s time to change the notion that treatment for early-stage EGFR-mutated lung cancer ends after surgery, since recurrence rates are still very high even after adjuvant chemotherapy,” Masahiro Tsuboi, MD, PhD, director of the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East in Japan, and a principal investigator, said in a statement.
“These new data showing low rates of recurrence, particularly in the brain, combined with the remarkable disease-free survival benefit, clearly demonstrate that (osimertinib) provides patients with more time living cancer-free,” he said.
ESMO is expected to feature several trials with landmark results in lung cancer, which is the leading cause of cancer death. Most patients with lung cancer, 80% to 85%, have NSCLC.
Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non–small-cell lung cancer. N Engl J Med. Published online September 19, 2020. DOI: 10.1056/NEJMoa2027071