Durvalumab improves progression-free survival (PFS) by more than 11 months compared to standard of care and is the first medicine to show superior PFS in this setting
Data presented at the ESMO 2017 Congress follows FDA’s recent Breakthrough Therapy Designation for durvalumab in locally advanced, unresectable lung cancer
The PACIFIC trial continues to evaluate the other co-primary endpoint, overall survival
MISSISSAUGA, ON, September 9, 2017 – AstraZeneca and MedImmune, its global biologics research and development arm, have presented the full PFS data from a planned interim analysis of the Phase III PACIFIC trial. Results show that durvalumab demonstrated a statistically-significant and clinically-meaningful improvement in PFS compared to current standard of care with active surveillance in patients with locally-advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) who had not progressed following standard platinum-based chemotherapy concurrent with radiation therapy (CRT).1
Results of the Phase III PACIFIC trial, included at the Presidential Symposium I of the European Society of Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, show an improvement in PFS of more than 11 months in patients treated with durvalumab compared to placebo (full details in table below).1 The PFS improvement with durvalumab was observed across all pre-specified subgroups, including PD-L1 expression status. Patients receiving durvalumab also had a lower incidence of metastases than those receiving placebo.1 The PACIFIC trial continues to evaluate overall survival (OS), the other co-primary endpoint. Detailed results of the PACIFIC trial are published online in the New England Journal of Medicine.
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “The Phase III PACIFIC results are incredibly encouraging for a patient population that until now has been without treatment options. As the first Immuno-Oncology medicine to achieve improvement in progression-free survival in this setting, durvalumab is showing clear potential to become a new standard of care for patients with locally-advanced, unresectable NSCLC who have not progressed following chemoradiation.”
“These data represent a significant milestone in the treatment of Stage III non-small cell lung cancer,” says Dr. Mark Vincent, Professor of Oncology, University of Western Ontario and Consultant Medical Oncologist, London Regional Cancer Program. “For patients with tumours that are unresectable, prognosis is poor and options are limited. The demonstrated results of durvalumab in this trial may offer a new treatment option for some patients, harnessing the science of immuno-oncology to treat this disease.”
Summary of key efficacy results:1
|Endpoint||Study Arm||Value||Hazard Ratio (HR)/ Confidence interval (CI)|
|PFS* (first primary endpoint)||Durvalumab||16.8 months (median)||
95% CI, 0.42-0.65, p<0.0001
|Placebo||5.6 months (median)|
Duration of response (DoR)
|Objective Response Rate (ORR) as measured from baseline scan post-CRT completion||Durvalumab||28.4%||95% CI, 24.28-32.89, p<0.001|
|Placebo||16.0%||95% CI, 11.31-21.59, p<0.001|
* Time from randomization to the first documented tumour progression, or death in the absence of progression. Randomization in the PACIFIC trial occurred up to 6 weeks after completion of concurrent chemoradiation therapy (cCRT) and cCRT typically lasted at least 6 weeks. If the PFS had been measured prior to cCRT, it would add approximately 3 months or longer to the PFS value for each arm.
Among patients receiving durvalumab, the most frequent treatment-related adverse events (AEs) vs. placebo were cough (35.4% vs 25.2%), pneumonitis/radiation pneumonitis (33.9% vs 24.8%), fatigue (23.8% vs 20.5%), dyspnoea (22.3% vs 23.9%) and diarrhea (18.3% vs 18.8%). 29.9 per cent of patients experienced a grade 3 or 4 AE vs. 26.1 per cent for placebo, and 15.4 per cent of patients discontinued treatment due to AEs compared to 9.8 per cent of patients on placebo.1
On July 31, 2017, durvalumab received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) as a potential treatment for patients with locally advanced, unresectable NSCLC whose disease has not progressed following platinum-based chemoradiation therapy.2
AstraZeneca is in discussions with global health authorities regarding regulatory submissions for durvalumab based on the PACIFIC data. A status of regulatory submissions is usually provided with the Company’s quarterly results announcement.
Durvalumab received accelerated approval from the US Food and Drug Administration for previously treated patients with advanced bladder cancer and is under review in Canada and Australia for similar use.
Notes to Editors
About Locally Advanced (Stage III) NSCLC
Stage III lung cancer is divided into two stages (IIIA and IIIB), which are defined by how much the cancer has spread locally and the possibility of surgery.3 This differentiates it from Stage IV disease, when the cancer has spread (metastasized) to other organs.3
Stage III lung cancer represents approximately one-third of NSCLC incidence and was estimated to affect around 105,000 patients in the G7 countries in 2016.4 More than half of these patients have tumours that are unresectable. The current standard of care is chemotherapy and radiation followed by active surveillance to monitor for progression. The prognosis remains poor and long-term survival rates are low.1,5,6
The PACIFIC trial is a randomized, double-blinded, placebo-controlled, multi-centre, Phase III trial of durvalumab as sequential treatment in unselected patients with locally-advanced, unresectable (Stage III) NSCLC who have not progressed following platinum-based chemotherapy concurrent with radiation therapy.
The trial is being conducted in 235 centres across 26 countries involving approximately 700 patients. The co-primary endpoints of the trial are progression-free survival (PFS) and overall survival (OS), and secondary endpoints include landmark PFS and OS, objective response rate (ORR) and duration of response.
Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour's immune-evading tactics and inducing an immune response.2
Durvalumab continues to be studied in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in Immuno-Oncology. Durvalumab is being assessed in Phase III trials as a monotherapy in various stages of NSCLC, in small-cell lung cancer (SCLC), in metastatic urothelial cancer (mUC) and in head and neck squamous cell carcinoma (HNSCC). The combination of durvalumab and tremelimumab is being assessed in Phase III trials in NSCLC, SCLC, mUC and HNSCC and in Phase I/II trials in hepatocellular carcinoma and haematological malignancies.
About AstraZeneca in Lung Cancer
AstraZeneca is committed to developing therapies to help every patient with lung cancer. We have two approved therapies and a growing pipeline that targets genetic changes in tumour cells and boosts the power of the immune response against cancer. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.
About AstraZeneca’s Approach to Immuno-Oncology (IO)
Immuno-Oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. At AstraZeneca and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies will offer the potential for life-changing cancer treatments for the vast majority of patients.
We are pursuing a comprehensive clinical trial programme that includes durvalumab (anti-PD-L1) monotherapy and in combination with tremelimumab (anti-CTLA-4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small, targeted molecules from across our oncology pipeline, and with those of our research partners, may provide new treatment options across a broad range of tumours.
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology; Respiratory, Cardiovascular & Metabolic Diseases; and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK, and Mountain View, CA. For more information, please visit www.medimmune.com.
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of primary and specialty care medicines that transform lives. Our primary focus is on three important areas of healthcare: Cardiovascular and Metabolic disease; Oncology; and Respiratory, Inflammation and Autoimmunity. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, we employ more than 675 employees across the country and our AstraZeneca Canada headquarters are located in Mississauga, Ontario. For more information, please visit the company’s website at www.astrazeneca.ca.
Michelle Marchione, Senior Manager, Corporate Communications AstraZeneca Canada
1 Antonia S, et al. Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. The New England Journal of Medicine. 2017. Accessed September 8, 2017. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1709937#t=article
2 AstraZeneca. Imfinzi granted Breakthrough Therapy Designation by US FDA for patients with locally-advanced unresectable non-small cell lung cancer. Available at: https://www.astrazeneca.com/media-centre/press-releases/2017/imfinzi-granted-breakthrough-therapy-designation-by-us-fda-for-patients-with-locally-advanced-unresectable-non-small-cell-lung-cancer-31072017.html. Accessed on September 8, 2017.
3Canadian Cancer Society. Stages of non–small cell lung cancer. Available at: http://www.cancer.ca/en/cancer-information/cancer-type/lung/staging/?region=on. Access on September 8, 2017.
4 Aupérin A, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer.J Clin Oncol 2010;28:2181–90.
5 Yoon SM, et al. Therapeutic Management Options for Stage III Non-Small Cell Lung Cancer. World J Clin Oncol 2017;8:1–20
6 Ahn JS, et al. J Clin Oncol 2015; 33:2660–6.