The China National Medical Products Administration has approved osimertinib for use as an adjuvant treatment in patients with early-stage non–small cell lung cancer with EGFR exon 19 deletions or exon 21 mutations, following tumor resection with curative intent, with or without adjuvant chemotherapy as recommended by the patient’s physician.
The China National Medical Products Administration has approved osimertinib (Tagrisso) for use as an adjuvant treatment in patients with early-stage non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 mutations, following tumor resection with curative intent, with or without adjuvant chemotherapy as recommended by the patient’s physician.1
The regulatory decision was based on data from the phase 3 ADAURA trial (NCT02511106), where the EGFR TKI significantly improved disease-free survival (DFS), when used as adjuvant treatment in patients with stage IB/II/IIIA EGFR-mutated NSCLC. The median DFS per investigator assessment had not yet been reached in those given osimertinib vs 19.6 months in those given placebo (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).2
Moreover, in the overall study population, the median DFS had not yet been reached with osimertinib vs 27.5 months with placebo (HR, 0.20; 95% CI, 0.15-0.27; P <.0001).
“The expedited approval of [osimertinib] in China as part of a curative-intent regimen for early-stage EGFR-mutated lung cancer underscores the high unmet need in this setting and our commitment to improving outcomes in a country with one of the highest rates of EGFR mutations in the world,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, stated in a press release. “This approval reinforces the importance of EGFR testing across all stages of lung cancer, prior to treatment decisions, to ensure as many patients as possible can benefit from targeted therapies like [osimertinib] and live cancer-free longer.”
The trial enrolled a total of 682 patients with NSCLC that harbored EGFR exon 19 deletions or exon 21 L858R mutations who had complete tumor resection, with or without prior adjuvant chemotherapy. To be eligible for inclusion, patients had to have resectable tumors, stage IB-IIIA disease, predominant nonsquamous histology, and the aforementioned mutations which investigators prospectively identified from tumor tissue through the use of the cobas EGFR Mutation Test in a central laboratory.
Study patients were randomized in a 1:1 fashion to either oral osimertinib at 80 mg once daily or placebo after they recovered from surgery and standard adjuvant chemotherapy, if received.
The primary end point of the trial was DFS per investigator assessment, while key secondary end points included DFS in the overall study population; DFS at 2, 3, 4, and 5 years; overall survival (OS), safety, and health-related quality of life (HRQoL).
Earlier data presented during the 2020 ASCO Virtual Scientific Program indicated that the median DFS in a subgroup of patients with stage II/IIIA disease had not yet been reached with the EGFR TKI vs 20.4 months with placebo (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).3
At 2 years, the DFS rate in patients with stage IB disease was 87% with osimertinib vs 73% with placebo (HR, 0.50; 95% CI, 0.25-0.96). In patients with stage II disease, the 2-year DFS rates in the investigative and control arms were 91% and 56%, respectively (HR, 0.17; 95% CI, 0.08-0.31); in those with stage IIIA disease, these rates were 88% vs 32%, respectively (HR, 0.12; 95% CI, 0.07-0.20).
Although the OS data remain immature, at 5% maturity, the median OS has not yet been reached in either of the treatment arms (HR, 0.40; 95% CI, 0.18-0.90).
Data from an exploratory analysis of the trial, presented during the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer, revealed that adjuvant osimertinib improved DFS in this patient population, irrespective of prior adjuvant chemotherapy received or disease stage.4
In the overall population, osimertinib reduced the risk of disease recurrence or death by 84% in those who previously received adjuvant chemotherapy (HR, 0.16; 95% CI, 0.10-0.26); in those who had not received chemotherapy, the EGFR reduced the risk of disease recurrence or death by 77% (HR, 0.23; 95% CI, 0.13-0.40).
Another analysis presented during the meeting showed that HRQoL was maintained for patients with EGFR-mutated NSCLC who received adjuvant osimertinib vs placebo, with no clinically meaningful differences noted between the study arms.5
The most frequently experienced toxicities in those who were given osimertinib included laboratory abnormalities like lymphopenia, leukopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough.
In December 2020, the FDA approved adjuvant osimertinib 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; the decision was also based on data from ADAURA.
Osimertinib is also approved for use in the frontline treatment of patients with locally advanced or metastatic NSCLC harboring EGFR mutations and for the treatment of locally advanced or metastatic EGFR T790 mutation–positive NSCLCin China, the United States, Japan, the European Union, and other countries.