Osimertinib demonstrated statistically significant and clinically meaningful benefit as treatment of patients with stage Ib, II, and IIIA EGFR-mutant non–small cell lung cancer with complete tumor resection in the phase III ADAURA clinical trial.
Osimertinib (Tagrisso) demonstrated statistically significant and clinically meaningful benefit as treatment of patients with stage Ib, II, and IIIAEGFR-mutant nonsmall cell lung cancer (NSCLC) with complete tumor resection in the phase III ADAURA clinical trial (NCT02511106). Based on the efficacy findings, the study will be unblinded early under the recommendation from an Independent Data Monitoring Committee, according to a press release.1
According to AstraZeneca, developer of the drug, osimertinib did not lead to any additional safety concerns in the randomized, double-blinded clinical trial. Plans for regulatory submission are underway for osimertinib based on these findings. Data are expected to be presented at an upcoming medical meeting.
"We are thrilled by the recommendation to unblind the Phase III ADAURA trial much earlier than expected and are incredibly excited with these unprecedented results in patients with early-stageEGFR-mutated non-small cell lung cancer,” José Baselga, executive vice president, Oncology R&D, said in a statement. “Lung cancer is a devastating diagnosis and for the first time anEGFR-targeted medicine can now provide the hope of cure."
Osimertinib was compared with placebo for a treatment duration of up to 3 years. The primary end point is disease-free survival (DFS), and the key secondary end point is overall survival (OS). Other secondary end points include DFS at 2, 3, and 5 years; patient health-related quality of life and symptoms; and plasma concentrations.
ADAURA randomized 682 patients to receive either adjuvant osimertinib or placebo. Oral osimertinib tablets was administered at 80 mg once daily for 3 years or until disease recurrence. More than 200 sites in the United States, Europe, South America, Asia, and the Middle East conducted the study. Data readout is expected for the year 2022.
To be included in the study, patients underwent an MRI or CT scan of the brain prior to surgery, be classified as either stage IB, II, or IIIA, and confirmation of 1 of the 2 commonEGFRmutations associated with EGFR TKI sensitivity.
Patients were excluded from the study if they had any prior treatment with pre-operative or post-operative or planned radiation therapy for their current disease, pre-operative platinum-based or other chemotherapy, any anticancer therapy, or prior neoadjuvant or adjuvant EGFR TKI therapy. They also could not have had major surgery within 4 weeks of the first dose on study.
Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI), which is designed to inhibit bothEGFR-sensitizing andEGFRT790M-resistant mutations and has clinical activity against central nervous system metastases.
At the 2019 ESMO Congress, data were presented for the phase III FLAURA trial, which evaluated osimertinib in patients with metastaticEGFR-mutant NSCLC versus erlotinib (Tarceva) or gefitinib (Iressa). These findings demonstrated that OS was improved by 6.8 months with the study drug, inducing a median OS of 38.6 months (95% CI, 34.5-41.8) compared with 31.8 months (95% CI, 26.6-36.0) in the comparator arm.2
The FLAURA trial demonstrated a 20% reduction in the risk of death with osimertinib over erlotinib or gefitinib, and 54% of patients remained alive at 36 months compared with 44% of patients in the osimertinib and erlotinib/gefitinib arms, respectively. The agent also had better tolerability than erlotinib and gefitinib. Grade 3/4 toxicities occurred in 34% of patients receiving osimertinib compared with 45% receiving either of the first-generation TKIs.
Earlier findings from the FLAURA trial led tothe FDA’s approval of osimertinib as frontline treatment of patients withEGFR-mutant NSCLCin April 2018.
Both 40 mg and 80 mg doses of osimertinib have been previously approved for the frontline treatment of patients withEGFR-mutant advanced NSCLC in 80 countries, including the US, China, and the European Union. In addition, the EGFR TKI is approved in 87 countries for the treatment of patients with EGFR T790M-mutant advanced NSCLC, including the United States, Japan, China, and the European Union.1
Osimertinib is under development in combination with chemotherapy in the metastatic setting for the treatment of patients in the locally advanced unresectable disease in the FLAURA2 study (NCT04035486), as well as in combination with potential new medicines that addressed resistance to EGFR TKIs in the SAVANNAH (NCT03778229) and ORCHARD (NCT03944772) studies. The phase II SAVANNAH study combines osimertinib with savolitinib, and ORCHARD is a phase II study of osimertinib in combination with either savolitinib, gefitinib (Iressa), necitumumab (Portrazza), or platinum-based chemotherapy.