The combination of durvalumab and chemotherapy resulted in a statistically significant and clinically meaningful improvement in overall survival compared with chemotherapy alone when used in the first-line treatment of patients with advanced biliary tract cancer, meeting the primary end point of the phase 3 TOPAZ-1 trial.
The combination of durvalumab (Imfinzi) and chemotherapy resulted in a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy alone when used in the first-line treatment of patients with advanced biliary tract cancer, meeting the primary end point of the phase 3 TOPAZ-1 trial (NCT03875235).1
At the time of the predefined interim analysis, the regimen also resulted in improved progression-free survival (PFS) and overall response rate (ORR), which served as important secondary end points.
Additionally, durvalumab plus chemotherapy had favorable tolerability, with a toxicity profile that was comparable to what was observed in the control arm. Notably, the addition of the immunotherapy to chemotherapy did not result in more treatment discontinuation because of toxicities vs chemotherapy alone.
“Patients with advanced biliary tract cancer are in dire need of new treatment as progress in the first-line setting has remained largely stagnant for more than 10 years,” Do-Youn Oh, MD, PhD, principal investigator of TOPAZ-1 and professor in the Division of Medical Oncology, Department of Internal Medicine, at Seoul National University Hospital and Seoul National University College of Medicine, stated in a press release. “TOPAZ-1 is the first phase 3 trial to show that adding an immunotherapy to standard chemotherapy delivers a meaningful OS benefit for patients in this setting. Today’s exciting results are a major step forward in treating this disease and represent new hope for our patients.”
For the double-blind, placebo-controlled, multicenter, phase 3 TOPAZ-1 trial, investigators enrolled a total of 685 patients with unresectable advanced or metastatic biliary tract cancer, which included those with intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer.
To be eligible for enrollment, patients needed to have previously untreated disease if unresectable or metastatic disease at initial diagnosis. Patients recurrent disease more than 6 months following curative surgery or more than 6 months following completion of adjuvant therapy were also included.2 Patients had an ECOG performance status of 0 or 1.
If patients had a history of another primary malignancy, brain metastases or spinal cord compression, or uncontrolled intercurrent illness, they were excluded. Patients with ampullary cancer, those who had undergone a major surgical procedure within 28 days before the first dose of study treatment, or those who previously received locoregional therapy like radioembolization were also excluded.
Participants were randomized 1:1 to receive either durvalumab or placebo plus standard-of-care gemcitabine and cisplatin for up to 8 cycles, followed by durvalumab until disease progression.3 Stratification factors included disease status (initially unresectable vs recurrent) and primary tumor location.
The primary end point of the trial is OS, and key secondary end points include PFS, ORR, and duration of response per investigator assessment and RECIST v1.1 criteria. Investigators are also exploring the safety of the regimen.
“We are delighted TOPAZ-1 has been unblinded early due to clear evidence of efficacy for [durvalumab] plus chemotherapy, which has also demonstrated a strong safety profile,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a press release. “We have now delivered 2 positive gastrointestinal cancer trials in a row for [durvalumab], following the HIMALAYA trial [NCT03298451] in liver cancer. We believe the significant survival benefit demonstrated marks a new era of immunotherapy treatment in this devastating disease, and it advances our commitment to improving long-term survival for patients across these cancers where treatment options are limited.”
Previously, in December 2020, the FDA granted an orphan drug designation to the immunotherapy for use in patients with biliary tract cancer.
Data from TOPAZ-1 will be shared at an upcoming medical conference, as well as with health authorities, according to AstraZeneca.