Osimertinib Submitted for Priority Review in China for Adjuvant Treatment of EGFR-Mutated NSCLC Post-Surgery

By Feng Qiu

On October 12, AstraZeneca’s marketing application for osimertinib mesylate tablets in China was proposed for inclusion in the priority review program, for adjuvant treatment of adult patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) sensitizing mutations following tumor resection.

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor that simultaneously inhibits EGFR sensitizing mutations and the EGFR T790M resistance mutation. Compared with first- and second-generation EGFR-TKIs, it has enhanced blood-brain barrier penetration and demonstrates significant efficacy in patients with central nervous system metastases.

Osimertinib was first approved in China in March 2017 for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had experienced disease progression during or after prior treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), and whose tumors tested positive for the EGFR T790M mutation. On September 3, 2019, osimertinib mesylate tablets were approved for first-line treatment of adult patients with EGFR mutation-positive locally advanced or metastatic NSCLC. In October 2018, osimertinib was successfully included in Category B of the National Reimbursement Drug List through price negotiations, for use as a second-line therapy for advanced NSCLC. The reimbursement payment standards were set at RMB 510 per tablet (80 mg) and RMB 300 per tablet (40 mg), representing a price reduction of up to 70%, which significantly boosted its sales volume in China.

Following the sequential approval of new indications and its recommendation as the standard first-line treatment in the United States, the European Union, and Japan, osimertinib demonstrated strong sales performance. Its full-year 2018 sales revenue reached $1.86 billion, accounting for approximately 31% of AstraZeneca’s oncology business revenue. In 2019, this figure further rose to $3.189 billion, while its market performance in China also continued to climb.

Source: PharmaCube PharmaGo

Data from the Phase III ADAURA study presented at ESMO 2020 demonstrated that adjuvant osimertinib provided clinically meaningful improvements in central nervous system (CNS) disease-free survival (DFS) among patients with early-stage (Stage IB, II, and IIIA) EGFR-mutated non-small cell lung cancer (NSCLC) who had undergone complete tumor resection. Fewer patients in the osimertinib adjuvant therapy group experienced recurrence or death compared to the placebo group (11% vs. 46%). Among patients who experienced disease recurrence, 38% in the osimertinib group had metastatic recurrence, compared to 61% in the placebo group. Osimertinib significantly reduced the risk of CNS recurrence or death by 82% (HR 0.18). Median CNS DFS was not reached in either group.

Furthermore, a post hoc analysis suggested that among patients without prior recurrence at other sites, the estimated probability of brain disease recurrence at 18 months was less than 1% in those receiving osimertinib, compared with 9% in the placebo group. For the primary endpoint—disease-free survival in patients with stage II and IIIA disease—adjuvant therapy with osimertinib reduced the risk of disease recurrence or death by 83% (HR 0.17).