Adjuvant Osimertinib Yields Promising Reduction in Risk of Recurrence or Death in EGFR+ Stage IB-IIIA NSCLC

A 77% reduction in risk of disease recurrence or death, as well as an improved disease-free survival were observed following adjuvant treatment with osimertinib (Tagrisso) in patients with EGFR-mutant, stage II to IIIA non–small cell lung cancer (NSCLC) regardless of previous adjuvant chemotherapy or staging, according to updated data from the phase 3 ADAURA trial (NCT02511106).¹

Data presented during the 2022 ESMO Congress showed that at a median follow-up of 44.2 months (range, 0-67) with osimertinib (n = 233) and 19.6 months (range, 0-70) with placebo (n = 237), the median DFS was 65.8 months (95% CI, 54.4–not calculable [NC]) vs 21.9 months (95% CI, 16.6-27.5), respectively, in the population of patients with stage II/IIIA disease (hazard ratio [HR], 0.23; 95% CI, 0.18-0.30).

In the overall population, osimertinib (n = 339) resulted in a median DFS of 65.8 months (95% CI, 61.7-NC) vs 28.1 months (95% CI, 22.1-35.0) with placebo (n = 343), translating to a 73% reduction in the risk of disease recurrence or death (HR, 0.27; 95% CI, 0.21-0.34). In this group, the median follow-up for those who received osimertinib was 44.2 months (range, 0-69) and 27.7 months (range, 0-70) for those given placebo.

Notably, the DFS benefit provided by osimertinib over placebo was observed across all predefined subgroups. In those who received prior adjuvant chemotherapy (n = 410), the HR for DFS was 0.29 (95% CI, 0.21-0.39); the HR was 0.36 (95% CI, 0.24-0.55) in those who did not (n = 272). The HRs for those with stage IB (n = 212), stage II (n = 236), and stage IIIA (n = 234) disease per American Join Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 7th edition criteria were 0.41 (95% CI, 0.23-0.69), 0.34 (95% CI, 0.23-0.52), and 0.20 (95% CI, 0.14-0.29), respectively.

In a presentation at the congress, lead study author Masahiro Tsuboi, MD, of the Department of Thoracic Surgery and Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, added that the DFS benefit observed with osimertinib across disease stages was consistent following re-staged based on the AJCC/UICC 8th edition manual. In those with stage IB, II, and IIA disease, the HRs for DFS were 0.44 (95% CI, 0.25-0.76), 0.33 (95% CI, 0.21-0.50), and 0.22 (95% CI, 0.15-0.31), respectively.

“These updated data reinforce adjuvant osimertinib as the standard of care for patients with EGFR-mutated, stage IB to IIA NSCLC after complete tumor resection, with or without adjuvant chemotherapy,” Tsuboi said.

Patients who were at least 18 years of age (or at least 20 years of age in Japan/Taiwan) who had a World Health Organization (WHO) performance status of 0 or 1 and confirmed primary nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation were enrolled to ADAURA. Patients must have undergone a complete resection with negative margins.

The maximum interval between surgery and randomization on the trial was 10 weeks without adjuvant chemotherapy and 26 weeks with adjuvant chemotherapy.

Key stratification factors comprised disease stage (IB vs II vs IIIA), EGFR mutational status (exon 19 deletion vs L858R), and race (Asian vs non-Asian).

A total of 682 participants were randomly assigned to receive osimertinib at a once-daily dose of 80 mg or placebo administered, also administered once daily. The planned treatment duration for these patients was 3 years, and treatment continued until disease recurrence, treatment was completed, or discontinuation criterion were met.

Investigator-assessed DFS in patients with stage II/IIIA disease served as the primary end point of the trial; this was designed for superiority under the assumed HR of 0.70 for DFS. Important secondary end points included DFS in the overall population; DFS at 2, 3, 4, and 5 years; overall survival; safety; and health-related quality of life. Prespecified exploratory end points included patterns of recurrence and time to central nervous system (CNS) disease recurrence or death (CNS DFS).

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