Adjuvant Osimertinib Therapy Delays Disease Recurrence in Localized NSCLC

Targeted therapy osimertinib (Tagrisso) demonstrated significant improvements in disease-free survival in patients with localized non-small cell lung cancer (NSCLC) who were treated following surgery, according to new data presented in the 2020 American Society of Clinical Oncology Virtual Scientific Program. 

The findings, which come from an unplanned interim analysis of the phase 3 ADAURA trial, were presented by lead author Roy S. Herbst, MD, PhD, in a press briefing in advance of the annual meeting. 

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), is approved for the first-line treatment of patients with metastatic NSCLC with tumors that have EGFR mutations. The results from this study show efficacy in the adjuvant setting for patients with earlier stage disease and the same mutations. 

NSCLC represents 85% of all lung cancer cases, with an estimated 30% of patients presenting with resectable disease at diagnosis, according to Dr Herbst, who is the Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, and the Associate Cancer Center Director for Translational Research at Yale Cancer Center. Adjuvant chemotherapy is currently the standard of care for patients with resected stage II-IIIA NSCLC and select patients with stage IB disease; however, recurrence rates are high. 

The trial included 682 patients with primary non-squamous stage IB-IIIA NSCLC and confirmed EGFR mutation who were randomized to receive adjuvant osimertinib or placebo. Patients in the study had complete resection of primary NSCLC and were fully recovered from surgery. Patients in the osimertinib group took 80-mg tablets once daily, for up to 3 years, and postoperative chemotherapy was allowed. 

Overall, patients with stage II-IIIA had an 83% reduction in the risk of disease recurrence or death, according to the data. At 2 years, disease-free survival was 90% in the osimertinib group compared with 44% in the placebo group for patients with stage II-IIIA NSCLC with an EGFR mutation. In the overall population (stage IB-IIIA), osimertinib reduced the risk of disease recurrence or death by 79% compared with placebo. At 2 years, disease-free survival was 89% for those treated with osimertinib compared with 53% in placebo-treated patients. 

According to Herbst, adjuvant osimertinib is the first targeted agent in a global randomized trial to show statistically significant and clinically meaningful improvement in disease-free survival in this patient population.

The secondary end point, overall survival, was immature at the time of analysis. 

The safety profile of osimertinib in this study was consistent with its known safety profile and the drug was generally tolerable. 

According to Dr Herbst, the trial was a “home run.” 

“It’s an important advance to see a targeted therapy significantly delay disease recurrence following surgery in patients with non-small cell lung cancer. We can now treat patients earlier,” he said. 

References:

1. 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. Presented at: 2020 ASCO Virtual Scientific Program, May 29-31; online. Doi: 10.1200/JCO.2020.38.18_suppl.LBA5

2. Post-Surgery Osimertinib Delays Disease Recurrence in Patients With Localized Non-Small Cell Lung Cancer (NSCLC). News Release. ASCO; May 28, 2020. Accessed May 29, 2020. https://www.asco.org/about-asco/press-center/news-releases/post-surgery-osimertinib-delays-disease-recurrence-patients.