Instant Report

Date: 08-Jun-2021

AstraZenecas PACIFIC Phase III Trial Of Imfinzi Demonstrates Sustained Clinically Meaningful OS And PFS Benefit At 5 Years In Patient With Unresectabl

Updated results from the positive PACIFIC phase III trial showed AstraZeneca’s Imfinzi (durvalumab) demonstrated a sustained, clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit at five years in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed following concurrent chemoradiation therapy (CRT).

Lung cancer is the leading cause of cancer death accounting for about one-fifth of all cancer deaths, and 80-85% of patients with lung cancer have NSCLC. One in four patients with NSCLC are diagnosed at Stage III, where the majority of tumours are unresectable (cannot be removed with surgery). The approval of Imfinzi in this setting based on the results of this trial was the first new treatment to be available to these patients in decades.

Results from the updated post-hoc analyses showed an estimated five-year OS rate of 42.9% for patients treated with Imfinzi versus 33.4% for those on placebo after CRT. Median OS was 47.5 months for Imfinzi versus 29.1 for placebo. Following a maximum treatment course of one year, an estimated 33.1% of patients treated with Imfinzi had not progressed five years after enrolment versus 19% for placebo.

David Spigel, MD, chief scientific officer at the Sarah Cannon Research Institute, and investigator in the PACIFIC trial said, “This trial has once again set a new precedent in the treatment of patients with unresectable, Stage III non-small cell lung cancer. Historically, only 15-30% of these patients survived five years but these results show that with up to one year of treatment with Imfinzi, an estimated 43% of patients are still alive at five years. Moreover, three quarters of these patients had also not progressed in that time. This is a momentous achievement at the five-year landmark in this curative-intent setting.”

Dave Fredrickson, executive vice president, Oncology Business Unit, said, “Five-year survival is a clinically significant and emotionally meaningful milestone for people with cancer and their families, and it's incredible to see the majority of patients surviving that long have not progressed four years after completing treatment. These results – the first of their kind in Stage III unresectable lung cancer – reinforce the long-term benefit of Imfinzi as the established standard of care in this curative-intent setting. With trials like PACIFIC and our comprehensive development programme in early-stage disease across cancer settings, our strategy is to improve cancer outcomes by treating patients as early as possible, aiming to deliver life-changing treatments that increase the potential for cure.”

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after CRT in the US, Japan, China, across the EU and in many other countries. Since the first approval in February 2018, more than 80,000 patients in this setting have been treated with Imfinzi.

In 2020, an estimated 2.2 million people were diagnosed with lung cancer worldwide. Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC. Stage III NSCLC represents approximately one quarter of NSCLC incidence.

Stage III (locally advanced) NSCLC is divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally. In contrast to Stage IV, when cancer has spread (metastasised), the majority of Stage III patients are currently treated with curative intent.

The PACIFIC trial was a phase III, randomised, double-blinded, placebo-controlled, multi-centre trial of Imfinzi as treatment in ‘all-comer’ patients (regardless of PD-L1 status) with unresectable, Stage III NSCLC whose disease had not progressed following concurrent platinum-based CRT.

The trial was conducted at 235 centres across 26 countries involving 713 patients. The primary endpoints of the trial were PFS and OS, and secondary endpoints included landmark PFS and OS, objective response rate and duration of response. Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

In addition to approvals in the unresectable, Stage III NSCLC setting, Imfinzi is approved for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN phase III trial in the EU, US, Japan and many other countries around the world. Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, biliary tract cancer (a form of liver cancer), oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer and other solid tumours.