FDA Approval Summary: Osimertinib for Adjuvant Treatment of Surgically Resected Non–Small Cell Lung Cancer, a Collaborative Project Orbis Review

Abstract

On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non–small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study, in which 682 patients with NSCLC were randomized to receive osimertinib (n = 339) or placebo (n = 343). Disease-free survival (DFS) in the overall population (stage IB–IIIA) was improved for patients who received osimertinib, with an HR of 0.20; 95% confidence interval (CI), 0.15–0.27; P < 0.0001. Median DFS was not reached for the osimertinib arm compared with 27.5 months (95% CI, 22.0–35.0) for patients receiving placebo. Overall survival data were not mature at the time of the approval. This application was reviewed under FDA's Project Orbis, in collaboration with Australia Therapeutic Goods Administration, Brazil ANVISA, Health Canada, Singapore Health Sciences Authority, Switzerland Swissmedic, and the United Kingdom Medicines and Healthcare products Regulatory Agency. This is the first targeted therapy adjuvant approval for NSCLC and has practice-changing implications.

Structural Insight and Development of EGFR Tyrosine Kinase Inhibitors

“…Osimertinib underwent phase I trial in 2013 and was approved by the FDA two years later to be used for EGFR T790M-positive NSCLC patients. In 18 April 2018, AstraZeneca announced that osimertinib was approved as the first-line treatment for patients with mutated EGFR (exon 19 deletion or exon 21 L858R substitution) [ 108 ]. In contrast, olmutinib, which was developed before Osimertinib, was withdrawn several months after its approval in South Korea due to the occurrence of Stevens–Johnson syndrome and consequent patient death [ 109 ].…”

Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers

“…Lung cancer has developed into one of the most common malignant tumors in the world, with the highest incidence and mortality rate ( Jiang et al, 2021a ; Drusbosky et al, 2021 ). The incidence of lung cancer has been on the rise due to factors such as smoking and environmental pollution ( Koch et al, 2021 ; Raguraman et al, 2021 ). Developed a label-free, highly sensitive method for exosome classification by combining SERS technology with statistical algorithms ( Park et al, 2017 ).…”

Deconstructing ADAURA: It is Time to Forgo Adjuvant Platinum-Based Chemotherapy in Resected IB-IIIA EGFR+ NSCLC (Except with RB Alterations?) When Adopting Adjuvant Osimertinib

“…The US FDA in their approval of the use of 3 years of adjuvant osimertinib considered “DFS in ADAURA is statistically significant, is clinically meaningful, and provides evidence of effectiveness. Although data for OS are immature at the time of this interim analysis, there is no evidence of a detriment on OS, and a positive trend toward improvement in OS [(HR = 0.40; 95% CI: 0.18–0.89) abstracted from the manuscript text] was observed in patients treated with osimertinib.” 31 The US FDA also was neutral in the use of adjuvant chemotherapy based on the data from ADAURA. “Early-stage NSCLC is a life-threatening condition with high rates of disease recurrence after surgical resection with or without adjuvant chemotherapy.” “Exploratory analyses by receipt of adjuvant chemotherapy did not reveal a substantial difference in efficacy or safety results.” 31 The use of adjuvant platinum-based chemotherapy for resected early-stage NSCLC is based primarily on 4 positive randomized trials (IALT, ANITA, JBR-10, and CALGB9633) and supported by meta-analysis.…”

“…The US FDA in their approval of the use of 3 years of adjuvant osimertinib considered “DFS in ADAURA is statistically significant, is clinically meaningful, and provides evidence of effectiveness. Although data for OS are immature at the time of this interim analysis, there is no evidence of a detriment on OS, and a positive trend toward improvement in OS [(HR = 0.40; 95% CI: 0.18–0.89) abstracted from the manuscript text] was observed in patients treated with osimertinib.” 31 …”