Durvalumab Plus Chemotherapy Significantly Improves Survival in Biliary Tract Cancer

Patients with biliary tract cancer treated with the frontline combination of durvalumab (Imfinzi) and standard-of-care (SOC) chemotherapy had a statistically significant and clinically meaningful improvement in overall survival (OS) compared with chemotherapy alone, meeting the primary end point of the phase 3 TOPAZ-1 (NCT03875235) study.¹

AstraZeneca announced in a press release that the experimental combination also achieved 2 key secondary end points of the study: improvements in progression-free survival (PFS) and overall response rate (ORR). Durvalumab with SOC chemotherapy was also well-tolerated with similar safety to the control arm. No increase in treatment discontinuation was observed with the addition of durvalumab in the study.

Data from TOPAZ-1 will be announced during an upcoming medical meeting and shared with health authorities.

“Patients with advanced biliary tract cancer are in dire need of new treatments as progress in the 1st-line setting has remained largely stagnant for more than 10 years. TOPAZ-1 is the first phase 3 trial to show that adding an immunotherapy to standard chemotherapy delivers a meaningful overall survival 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,” said Do-Youn Oh, MD, PhD, professor, Division of Medical Oncology and principal investigator of TOPAZ-1, in a press release.

TOPAZ-1 is an ongoing randomized, double-blind placebo controlled, multi-regional, international study of 757 patients with unresectable advanced or metastatic biliary tract cancer including those with cholangiocarcinoma and gallbladder carcinoma. The study was conducted at 145 centers across 17 countries in the United States, Europe, South America, and Asia.^1,2

Patients enrolled received either durvalumab with gemcitabine and cisplatin administered by intravenous infusion for up to 8 cycles followed by monotherapy every 4 weeks until disease progression or discontinuation or a matching dose schedule of placebo with gemcitabine and cisplatin.

Other secondary end points investigated in the study included duration of response (DOR), quality of life, PFS, ORR, DOR, and disease control rate according to PD-L1 expression, serum concentration of durvalumab, and tiered results of anti-drug antibodies for durvalumab.

To be eligible for the study, patients must have had histologically confirmed disease, be previously untreated with recurrent disease more than 6 months after curative surgery or adjuvant therapy and have a WHO/ECOG performance score of 0 or 1. Patients with a history of another primary malignancy, brain metastases or spinal cord compression, and/or uncontrolled intercurrent illness were not eligible to enroll. Further, having a major surgical procedure within 28 days of the first dosing in the study or having undergone prior locoregional therapy were grounds for exclusion from the study.

“We are delighted TOPAZ-1 has been unblinded early due to clear evidence of efficacy for Imfinzi plus chemotherapy, which has also demonstrated a strong safety profile. We have now delivered two positive gastrointestinal cancer trials in a row for Imfinzi, following the HIMALAYA trial 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, Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, stated, in the press release.¹

Durvalumab, an anti-PD-L1 therapy, is currently FDA approved for indication in non–small cell lung cancer (NSCLC), and extensive-stage small cell lung cancer (SCLC). The agent is also being actively developed to treat other SCLC and NSCLC subgroups, as well as bladder cancer, liver cancer, esophageal cancer, gastric cancer, gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, biliary tract cancer, and other solid tumors.

_References:

_{1. Imfinzi plus chemotherapy significantly improved overall survival in 1st-line advanced biliary tract cancer in TOPAZ-1 phase III trial at interim analysis. News release. AstraZeneca October}

_{25, 2021. Accessed October 25, 2021. https://bit.ly/3b9lTYM}

_{2. Durvalumab or placebo in combination with gemcitabine/cisplatin in patients with 1st line advanced biliary tract cancer (TOPAZ-1) (TOPAZ-1). Clinicaltrials.gov. Accessed October 25, 2021. https://bit.ly/3EcnwBf}