China’s National Medical Products Administration has approved durvalumab plus gemcitabine and cisplatin for frontline use in adult patients with locally advanced or metastatic biliary tract cancer.
China’s National Medical Products Administration has approved durvalumab (Imfinzi) plus gemcitabine and cisplatin for frontline use in adult patients with locally advanced or metastatic biliary tract cancer.1
The regulatory decision was backed by findings from the global, phase 3 TOPAZ-1 trial (NCT03875235), in which treatment with durvalumab in combination with chemotherapy led to a 20% reduction in the risk of death vs placebo plus chemotherapy (HR, 0.80; 95% CI, 0.66-0.97; P = .021). The median overall survival (OS) was 12.8 months (95% CI, 11.1-14.0) in the durvalumab arm vs 11.5 months (95% CI, 10.1-12.5) in the placebo arm.2
Moreover, the median progression-free survival (PFS) in the durvalumab and placebo arms was 7.2 months (95% CI, 6.7-7.4) and 5.7 months (95% CI, 5.6-6.7), respectively (HR, 0.75; 95% CI, 0.63-0.89; P = .001). The investigator-assessed confirmed overall response rate (ORR) was 26.7% with durvalumab vs 18.7% with placebo (odds ratio, 1.60; 95% CI, 1.11-2.31).
Furthermore, data from a prespecified exploratory analysis cohort of patients from mainland China showed that the durvalumab combination reduced the risk of death by 22% compared with chemotherapy alone (HR, 0.78; 95% CI, 0.51-1.18; P = .238).3 This population achieved a median OS of 9.1 months (95% CI, 6.3-13.7) with durvalumab vs 9.2 months (95% CI, 7.1-10.2) with placebo. The median PFS was 4.7 months (95% CI, 3.1-6.4) and 4.4 months (95% CI, 3.1-5.4) with durvalumab and placebo, respectively (HR, 0.79; 95% CI, 0.52-1.19). The ORR was 12.3% in the durvalumab arm vs 9.2% in the placebo arm.
Additionally, in a cohort of patients from mainland China, Hong Kong, and Taiwan, the median OS was 10.0 months (95% CI, 7.9-13.6) with durvalumab vs 9.0 months (95% CI, 7.2-10.2) with placebo (HR, 0.80; 95% CI, 0.57-1.13). The median PFS was 5.6 months (95% CI, 4.1-7.3) and 4.5 months (95% CI, 3.4-5.5) with durvalumab and placebo, respectively (HR, 0.72; 95% CI, 0.52-1.01). The ORR was 15.6% in the durvalumab arm vs 12.2% in the placebo arm.
“Over the past decade, there has been little progress in the treatment of advanced biliary tract cancer,” Shukui Qin, MD, president of Nanjing Tianyinshan Hospital of China Pharmaceutical University in Nanjing, Jiangsu and the national leading principal investigator of TOPAZ-1 in China, stated in a press release.1“However, the successful results of the TOPAZ-1 trial confirmed that durvalumab plus routine chemotherapy has statistically significant and clinically meaningful OS and PFS benefits for these patients. This approval provides a new and better option for the treatment of these patients in China.”
The randomized, double-blind, multicenter TOPAZ-1 trial evaluated the efficacy and safety of durvalumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment in 685 patients with unresectable or advanced or metastatic biliary tract cancer, including gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The trial was conducted at 105 centers across 17 countries in North America, Europe, South America, and Asia. Patients were excluded if they had ampullary carcinoma.
Patients were randomly assigned 1:1 to receive either durvalumab or placebo plus gemcitabine and cisplatin for a maximum of 8 cycles, followed by monotherapy with durvalumab or placebo until progressive disease or unacceptable toxicity.2
OS served as the trial’s primary end point. Key secondary end points were PFS, ORR, and safety.
In the global population, the median duration of study treatment was 7.3 months (range, 0.1-24.5) with durvalumab vs 5.8 months (range, 0.2-21.5) with placebo. Respectively, 99.4% and 98.8% of patients in the durvalumab and placebo arms experienced any-grade adverse effects (AEs). Grade 3/4 AEs were observed in 75.7% of patients in the durvalumab arm vs 77.8% of those in the placebo arm. In total, 13.0% of patients in the durvalumab arm discontinued treatment because of AEs vs 15.2% of those in the placebo arm. Twelve patients in the durvalumab arm died because of AEs vs 14 patients in the placebo arm.
In the durvalumab arm, the most common AEs were anemia (48.2%), nausea (40.2%), constipation (32.0%), and neutropenia (31.7%). In the placebo arm, the most common AEs were anemia (44.7%), nausea (34.2%), and decreased neutrophil count (31.0%). Immune-mediated AEs occurred in 12.7% and 4.7% of patients in the durvalumab and placebo arms, respectively, with grade 3/4 immune-mediated AEs occurring in 2.4% and 1.5% of patients, respectively.
The safety findings in the cohort of Chinese patients were consistent with those observed in the overall global population.1
“With this approval for [durvalumab] plus chemotherapy, physicians will now be able to offer this global standard-of-care treatment to patients in China, where nearly 1 in 5 patients with biliary tract cancer are diagnosed,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, added in the press release. “This important milestone underscores our commitment to bring innovative medicines that transform survival outcomes to people across the globe living with aggressive gastrointestinal tumors such as biliary tract cancer.”
In September 2022, the FDA approved durvalumab plus gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancers, based on findings from TOPAZ-1.4 The combination was also approved for this population in Japan and the European Union in December 2022.5,6