Adjuvant Osimertinib Approved in Europe for Early-Stage EGFR+ NSCLC

The European Commission has approved osimertinib for the adjuvant treatment of adult patients with early-stage EGFR-mutated non–small cell lung cancer following complete resection with curative intent.

The European Commission has approved osimertinib (Tagrisso) for the adjuvant treatment of adult patients with early-stage EGFR-mutated non–small cell lung cancer (NSCLC) following complete resection with curative intent.1

The indication is specific to those with stage IB, II, and IIIA disease with exon 19 deletions or exon 21 (L858R) mutations.

The approval was based on findings from the phase 3 ADAURA trial, in which osimertinib showed a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis of patients with stage II and IIIA EGFR-mutant NSCLC (HR, 0.17), as well as in the overall study population (HR, 0.20).2

“In the early stages of lung cancer, where tumor resection is possible but recurrence is far too common, adjuvant Tagrisso has shown an unprecedented disease-free survival benefit for patients with EGFR mutations,” said Margarita Majem, MD, PhD, Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Spain. “I expect this approval will change clinical practice in the EU, as it heightens the critical importance of EGFR mutation testing across all stages of lung cancer to ensure as many patients as possible can benefit from targeted medicines like Tagrisso.

The recent approval means that osimertinib is now approved in the adjuvant setting in more than 50 countries, and additional global regulatory reviews are ongoing, noted AstraZeneca, the developer of osimertinib.

In the phase 3 ADAURA trial, investigators enrolled 682 patients with NSCLC that harbored EGFR exon 19 deletions or exon 21 L858R mutations, who had complete tumor resection, with or without previous adjuvant chemotherapy. Patients were randomized 1:1 to receive either oral osimertinib at 80 mg once daily or placebo following recovery from surgery and standard adjuvant chemotherapy, if administered.

To be eligible for enrollment, patients needed to have resectable tumors that was stage IB to IIIA, predominant nonsquamous histology, and the aforementioned mutations, which were prospectively detected from tumor tissue via the cobas EGFR Mutation Test in a central laboratory.

The primary end point is investigator-assessed DFS; secondary end points comprise DFS in the overall population; DFS at 2, 3, 4, and 5 years; overall survival (OS), safety, and health-related quality of life.

Initials findings were presented during the 2020 ASCO Virtual Scientific Program. Here the median DFS in patients with stage II to IIIA disease had not yet been reached with osimertinib arm vs 20.4 months with placebo (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).3

The median DFS was not yet reached vs 27.5 months in the investigative and control arms, respectively, in the overall population (HR, 0.20; 99.12% CI, 0.14-0.30; <.0001).

At 2 years, the DFS rates in stage IB disease were 87% vs 73% (HR, 0.50; 95% CI, 0.25-0.96), respectively, in patients who received osimertinib vs placebo. These rates were 91% vs 56%, respectively, in those with stage II disease (HR, 0.17; 95% CI, 0.08-0.31) and 88% vs 32%, respectively, in those with stage IIIA disease (HR, 0.12; 95% CI, 0.07-0.20).

Overall survival (OS) data remain immature; 29 patients died overall (9 on osimertinib and 20 on placebo). The median OS has not yet been reached in either arm (HR, 0.40; 95% CI, 0.18-0.90).

Regarding safety, the most frequent adverse effects in those who received osimertinib included laboratory abnormalities such as lymphopenia, leukopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.

“We know the earlier a patient’s cancer is detected and treated, the greater chance they may have of being cured, which is why this approval is significant,” said Dave Fredrickson, executive vice president, Oncology Business Unit of AstraZeneca. “For the first time, patients in the EU with EGFR-mutated lung cancer have a targeted, biomarker-driven treatment option available in the early stages of their disease that can help them live cancer-free longer.”


  1. Tagrisso approved in the EU for the adjuvant treatment of patients with early-stage EGFR-mutated lung cancer. News release. AstraZeneca. May 28, 2021. Accessed May 28, 2021.
  2. Wu Y-L, Tsu 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
  3. Herbst RS, Tsuboi M, John T, et al. Osimertinib as adjuvant therapy in patients (pts) with stage IB-IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol. 2020;38(suppl 15):LBA5. doi:10.1200/JCO.2020.38.18_suppl.LBA5