February 19, 2021
Despite the Positive Results The Trial Has Faced Some Criticism
- The ADAURA trial showed osimertinib improves disease-free survival and reduces recurrence risk in patients with early-stage EGFR-positive NSCLC
- In December 2020, the FDA approved osimertinib (brand name: TAGRISSO) for adjuvant therapy after gross total resection in patients with stage IB-IIIA EGFR-positive NSCLC
- The results may possibly overestimate the treatment effect as the DSMB stopped the trial early due to efficacy
Osimertinib (brand name: TAGRISSO) significantly improves disease-free survival and reduces the risk of recurrence in patients with epidermal growth factor receptor (EGFR)-positive early-stage non-small cell lung cancer (NSCLC) following a gross total resection when compared to placebo. The ADAURA trial, published this past October in The New England Journal of Medicine, suggests that osimertinib is an effective adjuvant treatment after complete tumor resection. However, the results may possibly overestimate the treatment effect as the Data and Safety Monitoring Board (DSMB) stopped the trial early due to efficacy.
While EGFR tyrosine kinase inhibitors (TKIs) like osimertinib have revolutionized the treatment of advanced NSCLC, less progress has been made against early-stage cancers. “I think ADAURA is the first positive trial in early-stage cancer in about 15 years,” Dr. Patrick Forde, thoracic oncologist at Johns Hopkins, tells SurvivorNet Connect. “With the hazard ratio of 0.17 for disease-free survival, it’s hard to argue with this.”
Although the results of the trial were positive some experts have warned the trial did not asses the outcome of overall survival which is usually considered the gold standard in early stage trials of adjuvant therapy. Outside of adjuvant osimertinib, chemotherapy has demonstrated an OS advantage in the adjuvant setting in resected lung cancers and many argue this outcome measurement should have been the primary outcome in the ADAURA trial.
Dr. Forde points out that the trial has faced some criticisms. For one thing, it wasn’t long enough to determine overall survival. “The challenge with that in lung cancer is that it needs very long follow-up — anything from seven to 10 years of follow-up before you actually get an answer.”
In addition, patients who had a CT scan at diagnosis could have had undetected brain metastases. “You may have been treating those brain metastases with osimertinib instead of preventing the relapse of the cancer,” Dr. Forde says. Another potential limitation is that the trial was stopped early, which can overestimate the efficacy of the treatment.
Based on the ADAURA trial results, in December 2020, the FDA approved osimertinib for adjuvant therapy after tumor resection in patients with EGFR-positive NSCLC. For these patients, Dr. Forde considers osimertinib a “viable option” following adjuvant chemotherapy. “I think the data are reasonably compelling and do show a significant disease-free survival advantage,” he says.