Adjuvant Osimertinib Gets Japanese Approval for Early-Stage, EGFR-Mutated NSCLC

The Japanese Ministry of Health, Labour, and Welfare has approved osimertinib (Tagrisso) for use as an adjuvant treatment in patients with EGFR-mutated non–small cell lung cancer (NSCLC).

The regulatory decision was based on data from the phase 3 ADAURA trial (NCT02511106), in which osimertinib significantly improved disease-free survival over placebo in patients with stage IB to IIIA, EGFR-mutated NSCLC (n = 470).²

Data showed that 90% (95% CI, 84%-93%) of patients in the osimertinib arm were alive and disease free at 24 months vs 44% (95% CI, 37%-51%) of those in the placebo arm (overall HR, 0.17; 99.06% CI, 0.11-0.26; P < .001); this translated to an 83% reduction in the risk of disease recurrence or death. The median disease-free survival (DFS) was not yet reached (95% CI, 38.8–not calculable [NC]) in the investigative arm vs 19.6 months (95% CI, 16.6-24.5) in the control arm.

In the overall population, the percentage of patients who were alive and disease free at 24 months in the osimertinib and placebo arms were 89% (95% CI, 85%-92%) and 52% (95% CI, 46%-58%), respectively (overall HR, 0.20; 99.12% CI, 0.14-0.30; P < .001); this translated to an 80% reduction in the risk of disease recurrence or death. In the investigative arm, the median DFS was not yet reached (95% CI, NC-NC); the median DFS was 27.5 months (95% CI, 22.0-35.0) in the control arm.

“Osimertinib was first approved in Japan over 6 years ago and it has since played a critical role in our treatment of patients with lung cancer, particularly given the high prevalence of EGFR mutations among Japanese patients,” Masahiro Tsuboi, MD, PhD, chief and director in the Department of Thoracic Surgery & Oncology at National Cancer Center Hospital East, stated in a press release. “The approval of osimertinib for early-stage lung cancer means these patients will now have, for the first time, a targeted therapy option available earlier in their treatment journey, after surgery and chemotherapy as indicated.”

ADAURA enrolled patients with primary nonsquamous NSCLC with postsurgical pathological stage IB, II, or IIIA disease and a centrally confirmed EGFR mutation who were at least 18 years of age and had a World Health Organization performance status of 0 or 1.

Study participants were randomly assigned to 1:1 to receive osimertinib at a once-daily dose of 80 mg or placebo for 3 years. Key stratification factors were disease stage (IB vs II vs IIIA), EGFR mutational status (exon 19 del vs L858R), and race (Asian vs non-Asian).

The primary end point of the trial was DFS per investigator assessment in those with stage II to IIIA disease. Secondary end points comprised DFS in the overall population, overall survival, health-related quality of life, and safety.

The benefit achieved with osimertinib over placebo was noted across all predefined subgroups. In patients with stage IB disease, 88% (95% CI, 78%-94%) of those who received osimertinib vs 71% (95% CI, 60%-80%) of those who received placebo were alive and disease free at 24 months (overall HR, 0.39; 95% CI, 0.18-0.76). In those with stage II disease, these rates were 91% (95% CI, 82%-95%) and 56% (95% C I, 45%-65%), respectively; in those with stage IIIA disease, these rates were 88% (95% CI, 79%-94%) and 32% (95% CI, 23%-41%), respectively (overall HR, 0.12; 95% CI, 0.07-0.20).

In those who received adjuvant chemotherapy, 89% (95% CI, 83%-93%) and 49% (95% CI, 41%-56%) of those in the osimertinib and placebo arms, respectively were alive and disease free at 24 months (overall HR, 0.16; 95% CI, 0.10-0.26). In those who did not receive adjuvant chemotherapy, these rates were 89% (95% CI, 81%-94%) and 58% (95% CI, 49%-67%), respectively (HR, 0.23; 95% CI, 0.10-0.40).

Moreover, at 24 months, 98% (95% CI, 95%-99%) and 85% (95% CI, 80%-89%) of patients in the osimertinib and placebo arms, respectively, were alive and without central nervous system (CNS)–related disease (overall HR, 0.18; 95% CI, 0.10-0.33); this translated to an 82% reduction in the risk of CNS disease recurrence or death with osimertinib. The median CNS DFS was not yet reached (95% CI, 39.0-NC) in the investigative arm and 48.2 months (95% CI, NC-NC) in the control arm.

No new safety concerns were reported.

Final DFS data from ADAURA will be shared at the 2022 ESMO Congress.

References

1. Tagrisso approved in Japan for the adjuvant treatment of patients with early-stage EGFR-mutated lung cancer. News release. AstraZeneca. August 25, 2022. Accessed August 25, 2022. https://bit.ly/3chiEmo
2. Wu Y-L, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071