A subgroup analysis of Korean patients from the pooled data of two global phase II trials, AURA extension and AURA2, has found that osimertinib is as safe and effective in this subgroup of patients with pretreated EGFR-mutated advanced non-small cell lung cancer with T790M positive status as it was in the parent trials.
A subgroup analysis of Korean patients from the pooled data of two global phase II trials, AURA extension and AURA2, has found that osimertinib is as safe and effective in this subgroup of patients with pretreatedEGFR-mutated advanced non-small cell lung cancer (NSCLC) with T790M positive status as it was in the parent trials.1
According to the new study, which was published inCancer Research and Treatment, 66 Korean patients received osimertinib treatment and completed a median 19 months of treatment. Among the 62 patients with an evaluable response, the objective response rate (ORR) was 74% (95% confidence interval [CI], 61.5-84.5). The median duration of response was 9.8 months (95% CI, 7.1-16.8).
These results are comparable to those from the global phase II pooled analysis from AURA extension and AURA2 studies.2-4The global ORR for treatment with osimertinib was 66%, and the median duration of response was 12.3 months.
The authors, led by Myung-Ju Ahn, MD, of the Sungkyunkwan University School of Medicine in Seoul, South Korea, focused on Korean patients due to the significantly higher rate ofEGFR-mutated NSCLC among Asian patients compared with Caucasian patients, they wrote.
“The efficacy results of the current analysis in a Korean population are consistent with the global population, with ORR slightly higher,” they wrote. “This confirms that the efficacy of osimertinib is not different in patients of Korean ethnicity, and supports the recommendation for use of osimertinib in Korean patients with T790M-positive advanced NSCLC following disease progression after EGFR TKI therapy.”
AURA extension (NCT01802632) and AURA2 (NCT02094261) enrolled adult NSCLC patients with confirmed T790M positive status. Patients had a World Health Organization performance status of 0 or 1. They also had experienced disease progression following previous EGFR-TKI therapy, and may have received additional treatment regimens.
Osimertinib was given as 80 mg once daily until disease progression or trial discontinuation. The protocol permitted ongoing use of osimertinib following disease progression as long as clinical benefits continued.
Both AURA extension and AURA2 used ORR as their primary endpoints. Duration of response, progression-free survival (PFS) and tumor shrinkage were secondary endpoints. Both trials relied on blinded independent central reviewers for assessments, which included imaging every 6 weeks from baseline to disease progression.
Sixteen percent of the total patient populations in the AURA extension and AURA2 trials were Korean (n = 66 of 411). In AURA extension, 41 of 201 patients were Korean, while AURA2 included 25 Koreans out of 210 patients. Of the combined pool, 70% of patients were female and the median age was 60.5 years. Nearly three fourths of patients (73%) were never-smokers. Seventy percent had most recently taken an EGFR-TKI, while slightly more than half (56%) had previously taken platinum-based chemotherapy.
In addition to the ORR of 74%, the investigators found that 2 of 62 evaluable patients (3%) experienced a complete response. In the rest of the cohort, 44 patients (71%) had a partial response, while 13 patients (21%) had stable disease. The evaluable cohort also featured a disease control rate (DCR) of 95% (n = 59 patients; 95% CI, 86.5-99.0). Ahn et al found that, among the 46 patients who had an observed response, the median time to response was 5.6 weeks from the initial dose.
The primary data cutoff occurred in November 2016, when the median follow-up duration was 9.6 months. By the time of the extended data cutoff in May 2018, the median duration of exposure had increased to 19.3 months (range, 0.5 to 46.0 months; mean, 20.3 months). The median PFS in the FAS was 10.9 months (95% CI, 8.3-15.0.). Additionally, PFS data showed that 80% of patients were alive and progression-free at 6 months. PFS rates decreased to 46% at 12 months and then to 20% at 24 months.
As of the 2018 data cutoff, the median follow-up had reached 27.9 months, and two thirds of the patients (67%, n = 44) had died. At that time, the median overall survival (OS) was 29.2 months (95% CI, 24.8-35.7). One year OS was 83%, while 2-year OS was 64% and 3-year OS was 37%.
Every patient had at least one adverse event (AE). About one third of patients 35%, n = 23) experienced a grade 3 or higher AE. Rashes were the most common AEs (53%), followed by cough (33%), and then paronychia, diarrhea, and appetite loss (each 32%). One patient each developed mild interstitial lung disease and pneumonitis that were determined to perhaps be related to osimertinib, but these AEs resolved with treatment discontinuation.
Additionally, 8 of the 66 patients had central nervous system (CNS) metastases and were evaluable for response. None of these patients showed CNS progression.
Study limitations include the relatively small sample of Korean patients in the parent trials. “However, the efficacy, safety, and tolerability profiles of osimertinib in this Korean subgroup were consistent with the global phase II studies, which is indicative of the broadly beneficial effects of osimertinib in the wider Korean population,” Ahn et al wrote.