Imfinzi (durvalumab) förbättrar PFS vid NSCLC visar PACIFIC-studien

AstraZeneca presents superior progression-free survival for Imfinzi in the PACIFIC trial of patients with locally-advanced unresectable lung cancer

Imfinzi 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 Imfinzi in locally advanced, unresectable lung cancer

The PACIFIC trial continues to evaluate the other primary endpoint, overall survival

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 Imfinzi (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).

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 Imfinzi compared to placebo (full details in table below). The PFS improvement with Imfinzi was observed across all pre-specified subgroups, including PD-L1 expression status. Patients receiving Imfinzi also had a lower incidence of metastases than those receiving placebo. The PACIFIC trial continues to evaluate overall survival (OS), the other 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, Imfinzi is showing clear potential to become a new standard of care for patients with locally-advanced, unresectable NSCLC who have not progressed following chemoradiation.”

Dr. Luis Paz-Ares, Principal Investigator of the PACIFIC trial, from the Hospital Universitario Doce de Octubre, Madrid, Spain, said: “For patients with locally-advanced unresectable NSCLC who have completed chemoradiation therapy, Imfinzi represents a potential new treatment option in the context of clear unmet clinical need. Durvalumab overtly prolongs the period in which the disease is controlled with reasonable side effects. In addition, it offers hope to increase the cure rate in this setting, but more mature follow-up is needed to assess its impact on survival.”

Summary of key efficacy results:

Endpoint Medicine Value Hazard ratio (HR)/
Confidence interval (CI)
PFS*
(first primary endpoint)
Imfinzi 16.8 months (median) HR 0.52
95% CI, 0.42-0.65, p<0.0001
Placebo 5.6 months
(median)
Duration of response (DoR) Imfinzi Not reached N/A
Placebo 13.8 months
Objective Response Rate (ORR) as measured from baseline scan post-CRT completion Imfinzi 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 randomisation to the first documented tumour progression, or death in the absence of progression. Randomisation in the PACIFIC trial occurred up to 6 weeks after 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 Imfinzi, 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 diarrhoea (18.3% vs 18.8%). 29.9% of patients experienced a grade 3 or 4 AE vs. 26.1% for placebo, and 15.4% of patients discontinued treatment due to AEs compared to 9.8% of patients on placebo.

On 31 July 2017, Imfinzi 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.

AstraZeneca is in discussions with global health authorities regarding regulatory submissions for Imfinzi based on the PACIFIC data. A status of regulatory submissions is usually provided with the Company’s quarterly results announcement.

Imfinzi 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.

-ENDS-

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. This differentiates it from Stage IV disease, when the cancer has spread (metastasised) to other organs.

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. 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.

About PACIFIC

The PACIFIC trial is a randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi 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 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.

About Imfinzi

Imfinzi (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.

Imfinzi continues to be studied in multiple monotherapy trials and combination trials with tremelimumab and other potential new medicines in Immuno-Oncology. Imfinzi 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 Imfinzi 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.