Similar improvements in quality of life were found with frontline treatment of osimertinib for patients with advanced EGFR-mutant non–small cell lung cancer, as well as a clinically meaningful improvement in cough, compared with the standard-of-care EGFR TKIs, according to the phase III FLAURA trial. The results were presented at the 2018 European Lung Cancer Congress in Geneva, Switzerland.
Natasha Leighl, MD, FRCPC
Similar improvements in quality of life (QOL) were found with frontline osimertinib (Tagrisso) treatment for patients with advanced EGFR-mutant nonsmall cell lung cancer (NSCLC), as well as a clinically meaningful improvement in cough, compared with the standard of care (SOC) EGFR TKIs, according to the phase III FLAURA trial. The results were presented at the 2018 European Lung Cancer Congress (ELCC) in Geneva, Switzerland.1
The analysis used 2 QOL questionnaires for both treatment arms. Improvements in cough were recorded, with an adjusted mean change (AMC) from baseline in the osimertinib arm of -10.14 (95% CI, -12.2 to -8.16), deemed clinically relevant, compared with -8.18 (95% CI, -10.25 to -6.10) with SOC, consisting of erlotinib (Tarceva) or gefitinib (Iressa).
The mean difference was estimated between the 2 groups at -1.96 (P= .180). Improvement in cough was observed from the beginning of treatment in week 1 and was maintained until the first 9 months in both arms.
Changes from baseline for other key symptoms favored osimertinib versus SOC. These included chest pain (AMC, -6.8 vs -3.9, respectively), appetite loss (AMC, -5.8 vs -4.4), and dyspnea (AMC, -3.2 vs -1.2). The changes from baseline for fatigue were equal in both arms (AMC, -3.3 vs -3.3). However, apart from chest pain (P= .021), these differences were not considered statistically significant.
“Both treatment arms showed improvements in key symptoms from baseline over the first 9 months, with no significant differences in least-squares mean changes between the osimertinib and SOC arm,” Natasha Leighl, MD, FRCPC, a medical oncologist at Princess Margaret Hospital, Toronto, Canada, said while presenting this data. “These quality of life findings augment the efficacy and safety findings from FLAURA.”
She noted that 556 patients were enrolled in the FLAURA trial withEGFR-positive locally advanced or metastatic NSCLC were randomized to osimertinib (n = 279) or SOC (n = 277). Significant improvement was found in progression-free survival (PFS) with osimertinib compared to SOC (18.9 vs 10.2 months). This translated to a 54% reduction in the risk of progression or death (HR, 0.46; 95% CI, 0.37-0.57;P<.001). Improvement in overall survival was observed with osimertinib compared to SOC (HR, 0.63; 95% CI, 0.45-0.88; P= .007).2
More than 60% of patients in both treatment cohorts completed QOL questionnaires at baseline with subsequent follow up, including the EORTC Quality of Life Questionnaire Core 30 items (EORTC-QLQ-C30), given at baseline and every 6 weeks thereafter, and the Lung Cancer 13 items (QLQ-LC13), administered at baseline and then weekly for 6 weeks followed by every 3 weeks. Scores for these tests ranged from 0 to 100, while higher scores represented greater symptom burden. An improvement of ≥10 points was considered clinically relevant. The prespecified key symptoms included cough, dyspnea, chest pain, fatigue, and appetite loss.
Mean baseline scores were found to be equivalent in the osimertinib and SOC arms regarding cough (32.8 vs 33.5), dyspnea (22.5 vs 25.0), chest pain (19.5 vs 20.8), fatigue (32.2 vs 35.8), and appetite loss (22.7 vs 25.6). The estimated differences after treatment with osimertinib versus SOC were -1.96 for cough (P= .180), -1.99 for dyspnea (P= .113), -2.96 for chest pain (P= .021), 0.81 for fatigue (P= .093), and -1.46 for appetite loss (P= .427).
There was also a trend toward greater improvement with osimertinib with the LQ-C30 functional and global health/quality of life scores and there were no clinically relevant differences between the cohorts, Leighl noted.
Median time from randomization to the first recorded clinically relevant deterioration of key lung cancer symptoms was found to be similar between the 2 treatment arms.
Simon Ekman, MD, PhD, from the Thoracic Oncology Center at Karolinska University Hospital in Stockholm, Sweden, said, “Only cough showed a clinically relevant change but the degree of change perceived to be clinically relevant could well differ between trials and patient populations, meaning that changes of 8 points could also be clinically relevant.”
He reviewed the safety analysis from the FLAURA trial and thought that grade ≥3 adverse events (AEs) were reported in fewer patients in the osimertinib arm than in the SOC arm (34% vs 45%), concluding that osimertinib was associated with a somewhat lower rate of AEs leading to permanent treatment discontinuation compared with an EGFR TKI (13% vs 18%). It was also noted that dose interruptions were similar between the groups, as were dose reductions.
The FDA granted osimertinib a priority review designation on December 18, 2017, based on results from the FLAURA trial. Under the priority review, the agency acts within 6 months of receiving an application, rather than the standard 10 months. This places a potential decision for the application in June 2018. Osimertinib has previously been approved as a second-line therapy for patient with NSCLC harboring the acquiredEGFRT790M resistance mutation following a frontline EGFR TKI.