Adjuvant Osimertinib Elicits OS Improvement in Early-Stage EGFR-Mutated NSCLC

Osimertinib (Tagrisso) produced a statistically significant and clinically meaningful improvement in overall survival (OS) compared with placebo as adjuvant treatment for patients with stage IB, II, or IIIA, EGFR-mutated non–small cell lung cancer (NSCLC) after complete tumor resection with curative intent, according to updated results from the phase 3 ADAURA trial (NCT02511106).¹

Updated safety findings from the ADAURA trial were consistent with the established profile of the agent, and no new safety signals were reported. The data will be presented at an upcoming medical meeting.

“These new survival data for osimertinib reinforce the unprecedented ADAURA disease-free survival [DFS] results and confirm its potential to extend patients’ lives in early-stage disease,” Roy S. Herbst, MD, PhD, deputy director and chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, and principal investigator of the ADAURA trial, stated in a press release. “The ADAURA results provide powerful evidence that osimertinib offers the best possible care for patients with early-stage EGFR-mutated NSCLC who historically faced high rates of recurrence and previously had no targeted options after surgery.”

In December 2020, the FDA approved osimertinib for use as an adjuvant treatment following tumor resection in patients with NSCLC whose tumors harbor EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test, based on previously reported data from the ADAURA trial.² In patients with stage IB/II/IIIA EGFR-mutated NSCLC, osimertinib produced a median DFS that had not yet been reached (NR; 95% CI, 38.8-not estimable [NE]) compared with 19.6 months (95% CI, 16.6-24.5) for placebo (HR, 0.17; 95% CI, 0.12-0.23; P < .0001). In the overall study population, the median DFS was not reached (95% CI, NE-NE) in patients on the osimertinib arm compared with 27.5 months (95% CI, 22-36) on the placebo arm (HR, 0.20; 95% CI, 0.15-0.27; P < .0001).

Updated data presented at the 2022 ESMO Congress showed that in patients with stage II/IIIA disease, 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]) for osimertinib vs 21.9 months (95% CI, 16.6-27.5) for placebo (HR, 0.23; 95% CI, 0.18-0.30).³

In the overall population at a median follow-up of 44.2 months (range, 0-69) and 27.7 months (range, 0-70) for osimertinib and placebo, respectively, patients in the osimertinib arm (n = 339) experienced a median DFS of 65.8 months (95% CI, 61.7-NC) vs 28.1 months (95% CI, 22.1-35.0) for those in the placebo arm (n = 343; HR, 0.27; 95% CI, 0.21-0.34).

The phase 3 study enrolled patients at least 18 years of age (at least 20 years in Japan and Taiwan) who had confirmed nonsquamous stage IB, II, or IIIA NSCLC with or without adjuvant chemotherapy. Patients needed to have EGFR exon 19 deletions or exon 21 L858R mutations, brain imaging, and complete resection with negative margins. The maximum interval between surgery and randomization was 10 weeks for patients who did not receive adjuvant chemotherapy and 26 weeks for those given adjuvant chemotherapy.

Patients were randomly assigned 1:1 to receive osimertinib at 80 mg or placebo once daily. Stratification factors included stage (IB vs II vs IIIA), EGFR mutation (exon 19 deletion vs exon 21 L858R mutation), and race (Asian vs non-Asian). The planned duration of treatment was 3 years, and treatment continued until treatment completion, disease recurrence, or other discontinuation criteria were met.

Investigator-assessed DFS in the stage II/IIIA population served as the trial’s primary end point. Secondary end points included DFS in the overall population, DFS at 2, 3, 4, and 5 years, OS, safety, and health-related quality of life. Prespecified exploratory end points included patterns of recurrence and time to central nervous system disease recurrence or death.

“The ADAURA trial brought the first targeted medicine to patients with early-stage EGFR-mutated NSCLC,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a news release.¹ “These exciting OS results validate adjuvant [osimertinib] as the standard of care in this setting and reinforce the importance of early diagnosis and testing for EGFR [mutations] in lung cancer.”

References

1. Tagrisso demonstrated strong overall survival benefit in the ADAURA phase III trial for adjuvant treatment of patients with early-stage EGFR-mutated lung cancer. News release. AstraZeneca. March 9, 2023. Accessed March 9, 2023. https://www.astrazeneca.com/media-centre/
2. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. News release. FDA. December 18, 2020. Accessed March 9, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/
3. Tsuboi M, Wu YL, Grohe C, et al. Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): updated results from ADAURA. Ann Oncol. 2022;33(suppl 7):S1413-S1414. doi:10.1016/j.annonc.2022.08.047