Imfinzi Demonstrates Unprecedented Survival Benefit in Patients with Unresectable Stage III Lung Cancer, with 43% Achieving Five-Year Survival

SHANGHAI, June 5, 2021 /PRNewswire/ -- Updated follow-up results from the PACIFIC Phase III clinical trial, which previously reported positive results, show that AstraZeneca's Imfinzi (generic name: durvalumab; brand name: Imfinzi) demonstrated sustained and clinically meaningful overall survival (OS) and progression-free survival (PFS) benefits at five years in patients with Stage III unresectable non-small cell lung cancer (NSCLC) who did not experience disease progression following concurrent chemoradiotherapy (CRT).

Lung cancer is a leading cause of cancer-related mortality, accounting for approximately one-fifth of all cancer deaths. Among all lung cancer patients, 80–85% have non-small cell lung cancer.^1-3, one-quarter of non-small cell lung cancer patients are already at stage III at diagnosis, and most tumors are unresectable (cannot be surgically removed)^4,5. Based on the results of this clinical trial, the approval of durvalumab represents the first new therapy available to these patients in decades.^2,6,7。

The latest post-hoc analysis results show that following chemoradiotherapy, the 5-year overall survival (OS) rate was 42.9% in the durvalumab group compared with 33.4% in the placebo group. The median OS was 47.5 months for the durvalumab group and 29.1 months for the placebo group. Among patients with stage III unresectable non-small cell lung cancer (NSCLC) who received durvalumab for up to one year, 33.1% remained free of disease progression five years after enrollment, versus 19% in the placebo group. Following the publication of the primary progression-free survival (PFS) and OS analyses in *The New England Journal of Medicine* (NEJM) in 2017 and 2018, respectively, these updated data further confirm the sustained and significant benefit of durvalumab across these primary study endpoints.^8,9

Sarah CannonDr. David Spigel, Chief Scientific Officer of the institute and investigator for the PACIFIC clinical trial, stated: “This trial once again breaks new ground in the treatment of patients with stage III unresectable non-small cell lung cancer. Historically, only 15–30% of these patients survive five years. However, the aforementioned study results demonstrate that after up to one year of treatment with durvalumab, 43% of patients are still alive at five years. Moreover, three-quarters of these patients had not experienced disease progression at the five-year mark. This represents a treatment with curative intent asObjectiveIn the therapeutic field, significant achievements attained at the five-year milestone.”

Dave Fredrickson, Executive Vice President of AstraZeneca's Oncology Business Unit, said: "For cancer patients and their families, the five-year survival milestone is of both clinical and emotional significance. We are delighted to see that the majority of patients remain progression-free four years after completing treatment. The long-term benefit data recently announced for patients with stage III unresectable lung cancer strongly confirm that durvalumab has become the standard of care in the curative-intent treatment setting. Building on clinical trials such as PACIFIC and our comprehensive development programs across various early-stage cancers, our strategy is to intervene as early as possible to improve cancer outcomes, aiming to deliver life-changing therapies that increase the likelihood of a cure."

The primary analysis of overall survival (OS) in the Phase III PACIFIC trial revealed that the most common adverse reactions (incidence ≥20%) in the durvalumab and placebo groups included: cough (35.2% vs. 25.2%), fatigue (24.0% vs. 20.5%), dyspnea (22.3% vs. 23.9%), and radiation pneumonitis (20.2% vs. 15.8%). Grade 3 or 4 adverse reactions occurred in 30.5% of patients treated with durvalumab, compared with 26.1% in the placebo group; treatment was discontinued due to adverse reactions in 15.4% of patients in the durvalumab group versus 9.8% in the placebo group.⁹These data were presented on June 4 at the American Society of Clinical Oncology (ASCO) Annual Meeting.

Durvalumab has been approved in the United States, Japan, China, the European Union, and many other countries for the treatment of stage III unresectable non-small cell lung cancer with curative intent following chemoradiotherapy. Since its initial approval in February 2018, more than 80,000 patients have been treated with durvalumab.

AstraZeneca is conducting multiple registrational clinical trials of durvalumab for earlier-stage lung cancer, including potentially curative studies (Phase III clinical trials such as PACIFIC-2, PACIFIC-4, PACIFIC-5, MERMAID-1, MERMAID-2, AEGEAN, ADJUVANT BR.31, and ADRIATIC). AstraZeneca is also conducting two Phase II platform clinical trials for stage III unresectable non-small cell lung cancer (COAST) and early-stage neoadjuvant therapy (NeoCOAST) to evaluate innovative durvalumab-based combination therapies.

References:

1. 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 May 2021.

2. Cheema PK, et al. Perspectives on Treatment Advances for Stage III Locally Advanced Unresectable Non-Small-Cell Lung Cancer. Curr Oncol. 2019;26(1):37–42.

3. LUNGevity Foundation. Types of Lung Cancer. Available at  https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed May 2021.

4. EpiCast Report: NSCLC Epidemiology Forecast to 2025. GlobalData. 2016.

5. Provencio M, et al. Inoperable Stage III Non-Small Cell Lung Cancer: Current Treatment and Role Of Vinorelbine. J Thorac Dis. 2011;3:197-204.

6. Curran WJ, et al. Sequential vs Concurrent Chemoradiation for Stage III Non–Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452-1460.

7. Hanna N, et al. Current Standards and Clinical Trials in Systemic Therapy for Stage III Lung Cancer: What is New? Am Soc Clin Oncol Educ Book. 2015:e442-447.

8. Anthonia SJ et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377:1919-1929.

9. Antonia SJ, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018;379:2342-2350.

10. ASCO. Cancer.net. Lung Cancer – Non-Small Cell. Available at https://www.cancer.net/cancer-types/lung-cancer/view-all. Accessed May 2021.

AboutIIIStage Non-Small Cell Lung Cancer

In 2020, approximately 2.2 million people worldwide were diagnosed with lung cancer.¹。Lung cancer can be broadly classified into non-small cell lung cancer and small cell lung cancer, of which 80-85% are classified as non-small cell lung cancer.^2,3,5. Stage III non-small cell lung cancer accounts for approximately one quarter of all non-small cell lung cancer cases.⁴。

Based on the extent of local spread of cancer cells, stage III (locally advanced) non-small cell lung cancer can be divided into three subcategories (IIIA, IIIB, and IIIC). Unlike stage IV, where cancer cells have already spread (metastasized), most stage III patients are currently receiving treatment with curative intent.^5,10

AboutPACIFICResearch

The PACIFIC trial is a randomized, double-blind, placebo-controlled, international, multicenter, Phase III clinical trial evaluating durvalumab for the treatment of all patients with unresectable stage III non-small cell lung cancer (NSCLC) who did not experience disease progression following platinum-based concurrent chemoradiotherapy, regardless of PD-L1 expression status.

This clinical trial was conducted at 235 centers across 26 countries worldwide, enrolling a total of 713 patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary endpoints included milestone analyses of PFS and OS, objective response rate, duration of response, among others.

About Imfinzi

Imfinzi (durvalumab) is a humanized PD-L1 monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80, thereby inhibiting tumor immune escape and releasing the suppressed immune response.

In addition to its approval for Stage III unresectable non-small cell lung cancer, based on data from the Phase III CASPIAN clinical trial, Imfinzi has been approved in the European Union, the United States, Japan, and many other countries for the treatment of extensive-stage small cell lung cancer (ES-SCLC). Furthermore, Imfinzi has also been approved in multiple countries for the treatment of previously treated advanced bladder cancer.

As part of an extensive research and development program,IMFINZI®Currently, it is being investigated as monotherapy or in combination with other anticancer agents to explore its therapeutic potential in non-small cell lung cancer, small cell lung cancer, bladder cancer, liver cancer, cholangiocarcinoma (a type of liver cancer), esophageal cancer, gastric and gastroesophageal junction cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumors.

AstraZeneca's Lung Cancer Research

AstraZeneca is working to bring lung cancer patients closer to a cure through early detection and treatment, while continuously pushing the boundaries of science to improve the prognosis of drug-resistant and advanced lung cancer. By defining new therapeutic targets and researching innovative therapies, the company aims to deliver medicines to the patients who will benefit the most.

The Company's comprehensive portfolio covers leading lung cancer medicines and next-generation innovative drugs, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan, co-developed with Daiichi Sankyo; savolitinib, co-developed with HUTCHMED; and a pipeline of novel medicines and their combinations spanning various mechanisms of action.

AstraZeneca is a founding member of the global Lung Ambition Alliance, which is dedicated to accelerating innovation and delivering meaningful improvements in treatment and beyond for patients with lung cancer.

AstraZeneca's Oncology Immunotherapy Research

Cancer immunotherapy is a therapeutic strategy that works by activating the patient's immune system to attack tumors. Our immunotherapy drug portfolio is designed to overcome tumor-mediated immune suppression. AstraZeneca's investment in cancer immunotherapy reflects our commitment to delivering long-term survival benefits to new patient populations across various tumor types.

AstraZeneca is exploring a comprehensive clinical trial program evaluating durvalumab monotherapy, or durvalumab in combination with tremelimumab and other novel antibodies, across multiple tumor types, disease stages, and lines of therapy. Where appropriate, the PD-L1 biomarker will be utilized to guide treatment decisions, aiming to provide patients with optimal treatment strategies. Additionally, our immunotherapy agents in combination with radiotherapy, chemotherapy, and small-molecule targeted therapies from our company and partners hold the potential to deliver new treatment strategies to a broader population of cancer patients.

AstraZeneca's Research in Oncology

AstraZeneca is pioneering a revolution in oncology, committed to providing diverse oncology treatment solutions. By harnessing science to explore the complexity of cancer, we discover, develop, and deliver life-changing medicines to patients.

AstraZeneca’s Oncology business focuses on the most challenging cancers. Through continuous innovation, AstraZeneca has established an industry-leading, diversified portfolio and channels, continuously driving transformation in clinical practice and reshaping the patient experience.

AstraZeneca aims to redefine cancer treatment and conquer cancer in the future.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company focused on the research, development, manufacturing, and marketing of prescription medicines, with a primary focus on three major therapeutic areas: oncology, cardiovascular, renal & metabolism, and respiratory. Headquartered in Cambridge, UK, AstraZeneca operates in more than 100 countries, and its innovative medicines benefit millions of patients worldwide. For more information, please visithttp://www.astrazeneca.com。

Statement

Some uses of the drug in the studies have not yet been approved for any indication in China. AstraZeneca does not recommend the use of any unapproved medications.