Frontline treatment with osimertinib (Tagrisso) led to similar improvements in quality of life (QOL), including a clinically meaningful improvement in cough, compared with a standard of care (SOC) EGFR TKIs for patients with advanced
-mutant non–small cell lung cancer (NSCLC), according to findings from the phase III FLAURA trial presented at the 2018 European Lung Cancer Congress (ELCC).
In the analysis, which utilized 2 QOL questionnaires, both treatment arms reported improvements in cough, with an adjusted mean change (AMC) from baseline in the osimertinib arm of -10.14 (95% CI, -12.2 to -8.16), which was deemed clinically relevant, compared with -8.18 (95% CI, -10.25 to -6.10) with SOC, which consisted of erlotinib (Tarceva) or gefitinib (Iressa). The estimated mean difference between the 2 groups was -1.96 (P
= .180). The improvement in cough was observed beginning in treatment week 1 and was maintained throughout the first 9 months in both arms.
Changes from baseline for other key symptoms favored osimertinib versus SOC, including 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 the treatment 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,” presenter Natasha Leighl, MD, FRCPC, medical oncology, Princess Margaret Hospital, Toronto, Canada. “These quality of life findings augment the efficacy and safety findings from FLAURA.”
In the FLAURA trial, 556 patients with EGFR
-positive locally advanced or metastatic NSCLC were randomized to osimertinib (n = 279) or SOC (n = 277). There was a significant improvement in progression-free survival (PFS) seen with osimertinib compared with SOC (18.9 vs 10.2 months), which translated to a 54% reduction in the risk of progression or death (HR, 0.46; 95% CI, 0.37-0.57; P
<.001). Additionally, an improvement in overall survival was observed with osimertinib compared with SOC (HR, 0.63; 95% CI, 0.45-0.88; P
Of those enrolled in the study, more than 60% in both treatment cohorts completed QOL questionnaires at baseline with subsequent follow up. The questionnaires included 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 ranged from 0 to 100 with higher scores representing 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.
The mean baseline scores were equivalent in the osimertinib and SOC arms for 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). After treatment, the estimated treatment differences 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
While the QLQ-C30 functional and global health/quality of life scores also showed a trend toward greater improvement with osimertinib, 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 also similar between the two treatment arms. Invited discussant Simon Ekman, MD, PhD, Thoracic Oncology Center, Karolinska University Hospital in Stockholm, Sweden, pointed out that “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.”
Ekman also reviewed the safety analysis from the FLAURA trial and noted that grade ≥3 adverse events (AEs) were reported in fewer patients in the osimertinib arm than in the SOC arm (34% vs 45%). Additionally, Ekman said, osimertinib was associated with a somewhat lower rate of AEs leading to permanent treatment discontinuation compared with an EGFR TKI (13% vs 18%). Dose interruptions were similar between the groups, as were dose reductions.
In December 18, 2017, the FDA granted osimertinib a priority review designation, based on findings from the FLAURA trial. Under the priority review, the FDA acts within 6 months of receiving an application, rather than the standard 10 months, placing a potential decision for the application in June 2018. Osimertinib is currently approved as a second-line therapy for patient with NSCLC harboring the acquired EGFR
T790M resistance mutation following a frontline EGFR TKI.
- Leighl N, Karaseva N, Nakagawa K, et al. Patient-reported outcomes from FLAURA: Osimertinib versus standard of care (SoC) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC). Presented at: European Lung Cancer Congress; April 11-14, 2018; Geneva, Switzerland. Abstract 139PD.
- Soria J-C, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer. N Engl J Med. 2018;378:113-125. DOI: 10.1056/NEJMoa1713137.