Adjuvant Osimertinib in Patients With Stage IB to IIIA EGFR Mutation-Positive NSCLC After Complete Tumor Resection: ADAURA China Subgroup Analysis

Abstract

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People's Republic of China from ADAURA.

Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety.

Results: Of 682 patients enrolled globally, 159 patients in the People's Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13-0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17-0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21-1.20). HRQoL was maintained from baseline, and safety was consistent with the global population.

Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

Keywords: Adjuvant; China; EGFR; NSCLC; Osimertinib.

Figure 1

Patient disposition for the overall China population (stage IB–IIIA disease). Part 1 of screening comprised central EGFR mutation testing of tumor tissue for Ex19del or L858R mutations; part 2 of screening comprised confirmation of other eligibility criteria. Ex19del, exon 19 deletion.

Figure 2

Kaplan-Meier plot of DFS according to investigator assessment in (A) the China population of patients with stage II to IIIA disease and (B) the overall China population (stage IB–IIIA disease). DFS events are type of disease recorded as local/regional or distant or death. DFS events that do not occur within two scheduled visits (plus visit window) of the last assessable time point (or randomization) are censored and therefore excluded in the number of events. CI, confidence interval; DFS, disease-free survival; HR, hazard ratio; NC, not calculable; NR, not reached.

Figure 3

Subgroup analysis of DFS according to investigator assessment in the overall China population (stage IB–IIIA disease). The subgroup analysis was performed using a Cox proportional hazards model including treatment, subgroup, and a treatment-by-subgroup interaction term. Subgroup categories with less than 20 events were excluded from the analysis; this included the following subgroups: ^aage (≥65 y); ^bsmoking history (yes); ^cstage (IB); and ^dadjuvant chemotherapy (no). A hazard ratio less than 1 implies a lower risk of disease recurrence or death with osimertinib versus placebo. CI, confidence interval; Ex19del, exon 19 deletion.

Figure 4

Kaplan-Meier plot of OS in the overall China population (stage IB–IIIA disease). Data for patients not known to have died at the time of the analysis were censored at the last recorded date on which the patient was known to be alive. Median duration of follow-up for OS in patients whose data were censored was 63 months in both the osimertinib group and the placebo group. CI, confidence interval; HR, hazard ratio; NC, not calculable; NR, not reached; OS, overall survival.

Figure 5

Change in SF-36 (A) PCS and (B) MCS scores from baseline to week 156 in the overall China population (stage IB–IIIA disease). Error bars represent SDs. MCS, mental component summary; PCS, physical component summary; SF-36, short form-36 health survey.