NMPA Approves Tagrisso (Osimertinib) as First-Line Treatment for EGFR-Mutated Advanced NSCLC

On September 4, AstraZeneca announced that the China National Medical Products Administration (NMPA) has formally approved Tagrisso (osimertinib mesylate tablets) for first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.

Results from the Phase III FLAURA trial demonstrated positive overall survival (OS) outcomes for osimertinib as first-line treatment in EGFR mutation-positive advanced non-small cell lung cancer (NSCLC), compared with the previous standard of care (SoC), erlotinib or gefitinib. The median progression-free survival (mPFS) reached 18.9 months, representing an 8.7-month extension over existing standard EGFR-TKI therapy. Prior to this, the National Medical Products Administration (NMPA) granted osimertinib priority review status, based on the findings of the FLAURA trial, which were published in the New England Journal of Medicine (NEJM).

Dave Fredrickson, Executive Vice President of AstraZeneca and Head of the Oncology Business Unit, stated, “In China, approximately 30%–40% of patients with non-small cell lung cancer (NSCLC) harbor EGFR mutations. The results from the FLAURA clinical trial suggest that Tagrisso may become an important new standard of care for first-line treatment of patients with NSCLC.”

“We extend our gratitude to the National Medical Products Administration and relevant authorities for their unwavering commitment to addressing patient needs and ensuring that innovative treatment options benefit a broader patient population at the earliest possible stage,” said Mr. Wang Lei, Global Executive Vice President of AstraZeneca and President of International Operations and China. “In 2004, Iressa (gefitinib), as the first targeted therapy for advanced lung cancer in China, pioneered the era of precision medicine. In 2017, the approval of osimertinib as a second-line treatment extended targeted therapy options for patients with T790M mutation-positive advanced non-small cell lung cancer (NSCLC) who had developed resistance to prior treatments. Today, the approval of osimertinib as a first-line therapy brings greater survival opportunities and improved quality of life to every patient with EGFR-mutated advanced NSCLC. AstraZeneca will continue to uphold its ‘patient-centric’ commitment, actively implement the cancer prevention and control initiatives outlined in the Healthy China Action plan, and consistently introduce internationally advanced medicines and indications to China, thereby contributing to increased five-year cancer survival rates and enabling high-quality long-term survival with cancer.”

In the FLAURA clinical trial, first-line treatment with osimertinib demonstrated a statistically significant advantage and clinically meaningful improvement in progression-free survival (PFS) compared with standard EGFR-TKI therapy. The median PFS was 18.9 months in the osimertinib group versus 10.2 months in the control group (HR=0.46 [95% CI, 0.37–0.57]; p<0.0001). Furthermore, osimertinib showed a PFS benefit across all prespecified subgroups, including patients with central nervous system metastases.

Recently, AstraZeneca announced positive overall survival (OS) results in patients with EGFR mutation-positive advanced non-small cell lung cancer, demonstrating that osimertinib provides both statistically significant and clinically meaningful improvements in overall survival.

The FLAURA study showed that the safety profile of osimertinib was consistent with data observed in previous clinical trials. Overall, osimertinib was well tolerated, with the incidence of grade 3 or higher adverse events (AEs) being 34% in patients receiving osimertinib compared to 45% in the control group. The most commonly reported adverse reactions in patients treated with osimertinib included diarrhea (58%), rash/acne (58%), dry skin (36%), paronychia (35%), stomatitis (29%), fatigue (21%), and decreased appetite (20%).

The FLAURA clinical trial demonstrated that initiating treatment with osimertinib in patients with EGFR-mutated non-small cell lung cancer (NSCLC) results in longer progression-free survival, improved overall survival, and higher quality of life. Osimertinib as a first-line therapy has been approved in more than 70 countries and regions, including the United States, the European Union, and Japan. It is listed as a preferred recommended agent for first-line treatment of advanced EGFR mutation-positive NSCLC in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Non-Small Cell Lung Cancer, the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines, the Pan-Asia Lung Cancer Consensus, and the Japanese Lung Cancer Society Guidelines.

Osimertinib was first approved in China in March 2017 and was announced to be included in the National Reimbursement Drug List in October 2018. It is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have experienced disease progression during or after prior epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy and whose tumors test positive for the EGFR T790M mutation.

Lung cancer is the leading cause of cancer-related deaths in both men and women, accounting for approximately one-fifth of all cancer deaths, which exceeds the combined total of breast, prostate, and colorectal cancers. Lung cancer is typically classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC comprising 80%–85% of cases. Approximately 10%–15% of NSCLC patients in the United States and Europe harbor epidermal growth factor receptor mutations (EGFRm), whereas the prevalence among Asian patients is as high as 30%–40%. These patients exhibit particular sensitivity to treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which block signaling pathways driving tumor cell growth. About 25% of patients with EGFR-mutated NSCLC present with brain metastases at diagnosis, a proportion that increases to approximately 40% within two years post-diagnosis. The presence of brain metastases typically reduces median survival to less than 8 months.

Tagrisso (osimertinib mesylate tablets, AZD9291) is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that simultaneously inhibits EGFR sensitizing mutations and the EGFR T790M resistance mutation, and demonstrates clinical efficacy against central nervous system metastases.

Tagrisso 40 mg and 80 mg once-daily oral tablets have been approved in more than 70 countries and regions worldwide, including the United States, Japan, and the European Union, for first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. It has also been approved in over 80 countries and regions globally, including the United States, Japan, China, and the European Union, for second-line treatment of patients with advanced NSCLC positive for the EGFR T790M mutation. Currently, Tagrisso is being evaluated in multiple new clinical trials to explore its efficacy in adjuvant therapy for early-stage lung cancer (ADAURA), treatment of locally advanced unresectable lung cancer (LAURA), combination therapy with chemotherapy in advanced lung cancer (FLAURA2), and combination therapy with other potential novel agents (SAVANNAH, ORCHARD).

The FLAURA trial was designed to evaluate the efficacy and safety of once-daily oral osimertinib 80 mg versus comparator EGFR-TKIs (erlotinib [150 mg orally once daily] or gefitinib [250 mg orally once daily]) in patients with previously untreated, locally advanced or metastatic EGFR-mutated non-small cell lung cancer. This double-blind, randomized trial enrolled 556 patients from 29 countries.

AstraZeneca has a robust portfolio of approved drugs and late-stage clinical candidates for lung cancer, covering various stages, treatment lines, and mechanisms of action. We address the unmet treatment needs of patients with EGFR mutation-positive non-small cell lung cancer (NSCLC) through our marketed therapies, Iressa and Tagrisso, as well as ongoing Phase III clinical trials (ADAURA, LAURA, FLAURA, and FLAURA2) and exploratory combination Phase II clinical trials (SAVANNAH and ORCHARD). Approximately 10%-15% of NSCLC patients in Europe and the United States, and approximately 30%-40% of NSCLC patients in Asia, are expected to benefit from these treatments.

Meanwhile, AstraZeneca’s extensive oncology immunotherapy portfolio has also advanced to late-stage clinical development, targeting patients with lung cancer lacking known genetic mutations, who account for approximately three-quarters of all lung cancer cases. The anti-PD-L1 antibody IMFINZI (durvalumab) is currently being studied in patients with advanced lung cancer (including the Phase III trials POSEIDON, PEARL, and CASPIAN), as well as in patients with earlier-stage disease with curative intent (including the Phase III trials AEGEAN, PACIFIC-2, ADRIATIC, ADJUVANT BR.31, PACIFIC-4, and PACIFIC-5), both as monotherapy and in combination with tremelimumab and/or chemotherapy.

AstraZeneca has a long-standing heritage in oncology research. Our rapidly expanding portfolio of novel medicines is transforming patients’ lives and unlocking immense potential for the company’s future growth. With the launch of at least six new drugs between 2014 and 2020, and a robust R&D pipeline enriched by investigational small molecules and biologics, we are committed to establishing oncology as a key growth driver for AstraZeneca. Our research focuses on tumors in four disease areas: lung, ovarian, breast, and hematologic cancers. In addition to leveraging AstraZeneca’s core capabilities, we actively pursue innovative partnerships and external investments to accelerate the realization of our strategy, such as our investment in Acerta Pharma for hematologic malignancy research.

By leveraging four major scientific platforms—cancer immunotherapy, tumor driver genes and resistance mechanisms, DNA damage repair, and antibody-drug conjugates (ADCs)—and advocating for the development of personalized combination therapies, AstraZeneca aims to redefine cancer treatment and ultimately conquer cancer in the future.

AstraZeneca is a global, science-led biopharmaceutical company focused on the research, development, manufacturing, and marketing of prescription medicines, with a particular emphasis on three major therapeutic areas: oncology; cardiovascular, renal, and metabolism; and respiratory. With operations in more than 100 countries, AstraZeneca’s innovative medicines benefit millions of patients worldwide. For more information, please visit www.astrazeneca.com or follow @AstraZeneca on Twitter.

Since entering China in 1993, AstraZeneca has adhered to a science-led approach and prioritized innovation to meet the country’s growing health needs, striving to realize its ambitious vision of “pioneering innovation, benefiting patients, and becoming China’s most trusted healthcare partner.” Headquartered in Shanghai, AstraZeneca employs approximately 13,000 people across China. The company has established manufacturing bases in Wuxi and Taizhou, Jiangsu Province, and set up its China logistics center in Wuxi. In China, AstraZeneca focuses primarily on therapeutic areas with the most urgent patient needs, including respiratory, cardiovascular, metabolic, oncology, gastrointestinal, and renal diseases.

In 2017, AstraZeneca’s China Commercial Innovation Center was established in Wuxi, with the aim of exploring innovative integrated solutions for whole-disease management based on the Health Internet of Things (HIoT) and diagnosis-treatment integration. In the same year, AstraZeneca and SDIC Innovation jointly established Dizal (Jiangsu) Pharmaceutical Co., Ltd. to accelerate the local research and development of new drugs. In 2019, AstraZeneca announced its support for the Wuxi Municipal Government and Wuxi High-Tech Zone in building the Wuxi International Life Science Innovation Park, pooling global expertise to benefit patients in China.

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