Osimertinib Demonstrates Significant Clinical Benefit in Chinese Patients with Early-Stage EGFR-Mutated NSCLC: ADAURA China Subgroup Data Confirmed at ELCC 2022

ShanghaiApril 2, 2022PR Newswire -- The 2022 European Lung Cancer Congress (ELCC) officially announced on April 1 local timeAstraZeneca's Tagrisso (Generic Name: Osimertinib Mesylate Tablets)Data from the China subgroup analysis of the ADAURA Phase III clinical trial, which is used for adjuvant treatment in patients with early EGFR mutation-positive (Exon 19 deletion or Exon 21 (L858R) substitution mutation) non-small cell lung cancer (NSCLC) after complete resection. The published data shows that the efficacy and safety results of the overall China subgroup (IB-IIIA stage) population are consistent with the data reported for the global population. Adjuvant treatment with Osimertinib significantly reduces the risk of disease recurrence or death by 82%, demonstrating significant clinical benefit.^[1]。

NSCLC accounts for 85% of all lung cancers.^[2]Among them, approximately 30% of patients can be diagnosed early and have the opportunity for surgical resection, but disease recurrence in early-stage disease remains common. According to previous data, the five-year recurrence rates for patients with Stage IB, Stage II, and Stage IIIA are 45%, 62%, and 76%, respectively. ^[3]Adjuvant chemotherapy has long been the standard treatment for operable lung cancer patients. However, the clinical benefits of adjuvant chemotherapy are limited, and it only increases the 5-year survival rate of patients by approximately 5%.^[4]In addition, a large number of normal cells are also killed during the treatment process, with relatively severe side effects, adversely affecting the patient's quality of life and compliance.

In Chinese patients with NSCLC, nearly half of the patients have EGFR sensitizing mutations.^[5-7], early patients in this group can benefit early from postoperative adjuvant targeted therapy. Osimertinib has changed the clinical practice of early adjuvant treatment based on data from the ADAURA study, and in 2021 became the first targeted drug approved in China for adjuvant treatment of early-stage EGFR-mutated NSCLC patients. In the global ADAURA clinical study, osimertinib adjuvant therapy showed significant disease-free survival (DFS) benefits in Stage IB-IIIA EGFR mutation-positive NSCLC (hazard ratio [HR] 0.20), reducing the risk of distant recurrence, particularly decreasing the risk of central nervous system (CNS) progression (i.e., brain recurrence) or death by 82%.^[8]。

In the ADAURA study, patients were randomly assigned in a 1:1 ratio to receive either osimertinib (80 mg orally once daily) or placebo, including 159 Chinese patients (77 in the osimertinib group vs. 82 in the placebo group). In the Chinese subgroup of the ADAURA study, the risk of disease recurrence or death was reduced by 84% with adjuvant osimertinib treatment in patients with stage II-IIIA disease (median DFS: not reached [NR] in the osimertinib group vs. 18.3 months in the placebo group, HR=0.16, 95% confidence interval [CI]: 0.08, 0.31; p<0.0001; globally, the reduction in risk of disease recurrence or death was 83%, DFS HR=0.17). For patients with stage IB-IIIA disease, the risk of disease recurrence or death was reduced by 82% with adjuvant osimertinib treatment (median DFS: not reached [NR] in the osimertinib group vs. 24.9 months in the placebo group, HR=0.18, 95% CI: 0.10, 0.33; p<0.0001; globally, the reduction in risk of disease recurrence or death was 80%, DFS HR=0.20), consistent with the global population data.^[1],[9]Compared with the global population, the proportions of patients in the Chinese subgroup who were aged <65 years (global: 56% vs Chinese subgroup: 74%), at stage IB (global: 32% vs Chinese subgroup: 43%), and with L858R mutation (global: 45% vs Chinese subgroup: 58%) were all higher.^[1]Chinese patients have a higher proportion of receiving adjuvant chemotherapy compared to the global population (Global: 60% vs China subgroup: 66.7%).^[9]。

In addition, the safety results of osimertinib in the Chinese subgroup were consistent with the safety reported in the global ADAURA population and previous studies of osimertinib. In the Chinese subgroup, only 1 patient (1%) in the osimertinib group developed interstitial pneumonia (grade 2), and 5 patients (6%) experienced QTc prolongation.^[1]。

In summary, the efficacy and safety of adjuvant treatment with osimertinib in the Chinese subgroup are consistent with the global population, supporting 3-year adjuvant treatment with osimertinib as an effective treatment option for Chinese patients with stage IB-IIIA EGFR mutation-positive NSCLC after complete resection.^[1]。

Professor Wang Jie, Deputy Chairman of the Lung Cancer Professional Committee of the Chinese Anti-Cancer Association and Director of the Department of Internal Medicine at the Cancer Hospital of the Chinese Academy of Medical Sciences, stated: "The release of the ADAURA China subgroup analysis data is undoubtedly good news for Chinese patients with early-stage EGFR mutation-positive non-small cell lung cancer. First, this analysis is entirely based on Chinese patients receiving adjuvant treatment with osimertinib, making the data more relevant and meaningful for Chinese patients. Additionally, this means that the safety and efficacy of using osimertinib as an adjuvant treatment post-surgery have been fully validated by both the global ADAURA study results and the China subgroup results. As the only EGFR-TKI targeted drug to date that has demonstrated clinically meaningful DFS benefits in Chinese patients with Stage IB-IIIA non-small cell lung cancer, this data will further solidify osimertinib's position as the standard adjuvant treatment in China following complete resection of Stage IB-IIIA EGFR mutation-positive non-small cell lung cancer."

Currently, Osimertinib has been approved in over 50 countries and regions, including China, for adjuvant treatment post-surgery in patients with EGFR mutation-positive early-stage NSCLC, with applications for additional indications ongoing in other global regions. Osimertinib as an adjuvant therapy has been successively included in recommendations by major domestic and international guidelines such as the Chinese Medical Association, the Chinese Anti-Cancer Association, and the U.S. NCCN since 2021. Recently, it has also been recommended as the sole option following complete resection for stage IB-IIIA EGFR mutation-positive non-small cell lung cancer.^[1]Recommended inclusion in the 2022 ASCO Guidelines for Adjuvant Treatment of Resectable Stage I-III Non-Small Cell Lung Cancer (NSCLC). In addition, osimertinib has been approved in China, the United States, Japan, the European Union, and many other countries/regions for first-line treatment of patients with locally advanced or metastatic NSCLC who are EGFR mutation-positive, as well as for the treatment of patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation. Both indications have been included in the National Reimbursement Drug List, enhancing treatment accessibility for patients with advanced EGFR-mutated NSCLC.

AstraZeneca, with the original intention of "patient-centeredness," has always supported the development of lung cancer diagnosis and treatment in China. Since 2004, AstraZeneca has continuously introduced cutting-edge international innovative lung cancer drugs into China, committing to continuously improve the clinical benefits and accessibility of targeted lung cancer treatments. Osimertinib not only addresses the drug resistance issues of first- and second-generation targeted therapies through late-stage second-line treatment but also provides patients with longer survival benefits and higher quality of life through first-line treatment for advanced stages. Moreover, it further benefits earlier-stage lung cancer patients through adjuvant therapy post-surgery, offering them the possibility of a cure.。AstraZeneca will continue to drive innovation through relentless R&D efforts, advance medical practice transformation, enhance patient experiences, and pursue higher-quality long-term survival.

* "The only" refers to the fact that, as of March 2022, adjuvant treatment with osimertinib was the only recommended treatment in the 2022 ASCO Guideline for Adjuvant Treatment of Resectable Stage I-III Non-Small Cell Lung Cancer (NSCLC) for patients with Stage IB-IIIA EGFR mutation-positive NSCLC who have undergone complete resection.

References:

1.   Wang J et al. (2022) Adjuvant osimertinib in patients with stage IB–IIIA EGFR mutation-positive NSCLC after complete tumour resection: ADAURA China subgroup analysis. Poster presented at the 2022 European Lung Cancer Conference, Prague, The Czech Republic

2. Chinese Anti-Cancer Association, Lung Cancer Professional Committee. Guidelines for Adjuvant Treatment After Complete Resection of Stage I-III B Non-Small Cell Lung Cancer (2021 Edition). Chinese Medical Journal 2021; 101(16): 1132-42.

3.   Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol 2008;26:3552-3559.

4.   Wang Kun, Wu Yilong. IALT: The First Clinical Study to Prove That Adjuvant Chemotherapy After Complete Resection of Non-Small Cell Lung Cancer Improves Survival Rate[J]. Evidence-Based Medicine, 2004, 4(002):94-96.

5.   World Health Organization- International Agency for Research on Cancer. Globocan China Fact Sheet 2020. Available at http://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf. Accessed March 2021.

6.   Cheng, Y, et al. Osimertinib Versus Comparator EGFR TKI as First‑Line Treatment for EGFR‑Mutated Advanced NSCLC: FLAURA China, A Randomized Study. Targeted Oncology. 2021;16:165-176.

7.   World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed March 2021.

8.   Wu YL, et al. N Engl J Med. 2020 Oct 29;383(18):1711-1723

9.   Tagrisso Instructions, February 21, 2022 Edition