On April 16, 2024 Astrazeneca reported updated exploratory results from the TOPAZ-1 Phase III trial showed that Imfinzi (durvalumab) in combination with standard-of-care chemotherapy demonstrated a clinically meaningful long-term overall survival (OS) benefit at three years for patients with advanced biliary tract cancer (BTC) (Press release, AstraZeneca, APR 16, 2024, View Source [SID1234642077]).

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These results from TOPAZ-1, which are the longest survival follow-up ever reported for a global, randomised Phase III trial in this setting, will be presented on 18 April at the 2024 Cholangiocarcinoma Foundation Conference in Salt Lake City, Utah.

At more than three years (median follow-up of 41.3 months), results showed Imfinzi plus chemotherapy reduced the risk of death by 26% versus chemotherapy alone (based on a hazard ratio [HR] of 0.74; 95% confidence interval [CI], 0.63-0.87). The median OS was 12.9 months for Imfinzi plus chemotherapy versus 11.3 months for chemotherapy alone. More than twice as many patients on the Imfinzi-based regimen were alive at three years versus chemotherapy alone (14.6% versus 6.9%).

The TOPAZ-1 trial met the primary endpoint of OS in October 2021 at a planned interim analysis, showing that the combination reduced the risk of death by 20% versus chemotherapy alone (based on a HR of 0.80; 95% CI, 0.66-0.97; 2-sided p=0.021 at a statistical significance threshold of 0.03).

Do-Youn Oh, MD, PhD, Professor, Division of Medical Oncology, Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine, and principal investigator in the trial, said: "The latest data from TOPAZ-1 show that twice as many patients with advanced biliary tract cancer were still alive at three years with durvalumab and chemotherapy, an especially meaningful advance in a setting where historically the prognosis has been poor. These results reinforce the long-term benefit of this immunotherapy-based combination as a standard of care for patients with this devastating disease."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "TOPAZ-1 raised the bar for the treatment of advanced biliary tract cancer, showing a remarkable survival benefit for Imfinzi added to chemotherapy with a well-tolerated regimen. These data represent the longest survival follow-up reported for immunotherapy in this setting, and the three-year landmark survival improvement underscores our commitment to improving long-term outcomes in gastrointestinal cancers."

Stacie Lindsey, CEO, Cholangiocarcinoma Foundation said: "AstraZeneca’s longer survival data in advanced biliary tract cancer represents a meaningful milestone in that we are seeing three-year survival data for the first time for these patients. The data spurs hope that research will continue to improve outcomes for patients living with these challenging and rare cancers."

Summary of updated survival results: TOPAZ-1i

OSi,ii

Imfinzi + chemotherapy

(n=341)

Chemotherapy

(n=344)

Median OS (95% CI in months)

12.9

(11.6-14.1)

11.3

(10.1-12.5)

HR (95% CI) iii

0.74 (0.63-0.87)

OS rate at 36 months (95% CI) (%)iv

14.6

(11.0-18.6)

6.9

(4.5-10.0)

i. 26 months of additional follow-up (data cut-off: 23 October 2023) after the primary analysis, with 89% overall OS event maturity

ii. At data cut-off for this analysis, median (95% CI) follow-up time in all patients calculated using reverse Kaplan-Meier technique was 42.9 (39.8-44.3) months for Imfinzi plus chemotherapy and 41.8 (36.7-46.2) months for chemotherapy

iii. HR and 95% CI calculated using Cox proportional hazards model

iv. OS rates calculated using Kaplan-Meier technique

Imfinzi plus chemotherapy continued to be well-tolerated, with no new safety signals observed with longer follow-up. Results showed 15.4% of patients experienced treatment-related serious adverse events with Imfinzi plus chemotherapy versus 17.3% with chemotherapy alone.

Notes

Biliary tract cancer
Biliary tract cancer (BTC) is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).1,2 Approximately 50,000 people in the US, Europe and Japan and about 210,000 people worldwide are diagnosed with BTC each year.3-5 These patients historically have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years. For patients with metastatic disease, the five-year survival rate drops to less than 5%.7

Cholangiocarcinoma is more common in China and Thailand and is on the rise in Western countries.1,6 Gallbladder cancer is more common in certain regions of South America, India and Japan.8

Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.6,8,9

TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 adult patients with unresectable, locally advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to its indications in unresectable, Stage III NSCLC and ES-SCLC, Imfinzi is currently approved in a number of countries in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC.

Imfinzi is also approved in a number of countries in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in previously treated patients with advanced bladder cancer in a small number of countries.

Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. 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 SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal cancers and other solid tumours.