AURA3: Osimertinib improves lung cancer symptoms
Treatment with osimertinib significantly improves symptoms in patients with advanced non-small-cell lung cancer (NSCLC), according to new data from the phase III AURA3 trial presented at the European Lung Cancer Conference (ELCC) 2017.
The AURA3 trial included 419 patients with advanced, EGFR-mutant NSCLC who had progressed after first-line EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. Apart from the primary endpoint of progression-free survival (PFS), investigators also assessed patient-reported disease-specific symptoms using the European Organization for Research and Treatment of Cancer QLQ-LC13 questionnaire, as well as general cancer symptoms, functioning and global health status using QLQ-LC30. [ELCC 2017, abstract 85O_PR]
A significantly higher proportion of patients in the osimertinib arm had improvements in global health status compared with patients in the chemotherapy arm (37 vs 22 percent; odds ratio [OR], 2.11; p=0.007). Osimertinib treatment also significantly improved appetite (OR, 2.50) and fatigue (OR, 1.96) compared with chemotherapy.
In addition, osimertinib was associated with significantly longer time to deterioration of lung cancer symptoms, such as chest pain and dyspnoea. At the end of the study, chest pain was reported by 43.8 percent of patients in the osimertinib arm vs 58.4 percent of patients in the chemotherapy arm (hazard ratio [HR], 0.52; p<0.001), while dyspnoea was reported by 53.5 percent vs 73.7 percent of patients (HR, 0.42; p<0.001). Reduction in cough with osimertinib was not statistically significant (46 vs 54.7 percent; HR, 0.74; p=0.09).
“Osimertinib also significantly improved physical functioning, role functioning and social functioning scores compared with chemotherapy. There was a trend towards improved emotional and cognitive function with osimertinib, but the difference was not statistically significant vs chemotherapy,” reported lead author Dr Chee Lee of St George Hospital Cancer Care Centre, New South Wales, Australia.
Previously reported results of AURA3 showed significantly improved PFS with osimertinib vs chemotherapy (median, 10.1 vs 4.4 months; HR, 0.30; p<0.001). [N Engl J Med 2017;376:629-640]
“Patients in the AURA3 trial were receiving second-line therapy and were quite sick. For patients with incurable cancer, prolonging PFS probably has very little meaning. Treatment that can improve symptoms and maintain quality of life while prolonging PFS probably means a lot for them,” he continued.
“Patients with EGFR-mutant NSCLC should receive first-line EGFR-TKI treatment and second-line osimertinib therapy when they have a T790M resistance mutation. We need to know if there are options other than chemotherapy for third-line treatment,” said Professor Solange Peters of the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, who was not affiliated with the study.
“Osimertinib is effective in only 55 percent of EGFR-mutant NSCLC patients whose resistance to first-line EGFR-TKIs is caused by the T790M mutation. More research is needed to identify second-line treatment options that are better than chemotherapy in patients with different mechanisms of resistance,” she continued. “Researchers are also evaluating osimertinib in first-line treatment of all EGFR-mutant NSCLC in the phase III FLAURA trial, in which the third-generation EGFR-TKI is compared with gefitinib and erlotinib. Results will be reported later this year.”