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Durvalumab Addition Boosts Advanced Biliary Tract Cancer Survival

The TOPAZ-1 trial regimen of durvalumab plus gemcitabine and cisplatin chemotherapy has extended overall survival for patients with advanced biliary tract cancer
25 Jan 2022
Anticancer Agents;  Hepatobiliary Cancers;  Immunotherapy

Author: By Lynda Williams, Senior medwireNews Reporter 


medwireNews: Overall survival (OS) results from the TOPAZ-1 trial support the use of durvalumab alongside gemcitabine and cisplatin chemotherapy for the treatment of advanced biliary tract cancer, delegates were told at the 2022 ASCO Gastrointestinal Cancers Symposium in San Francisco, California, USA. 

“TOPAZ-1 is the first positive study in the first line in biliary tract cancers in a decade and sets a new potential standard of care of gemcitabine [plus] cisplatin [plus] durvalumab in unselected patients”, said session discussant Nilofer Azad, from Johns Hopkins University in Baltimore, Maryland, USA. 

Presenting author Do-Youn Oh, from Seoul National University Hospital in South Korea, explained that the phase III study was conducted in patients with locally advanced or metastatic, intrahepatic or extrahepatic cholangiocarcinoma or gallbladder cancer. Participants had treatment-naïve disease that was unresectable or metastatic at initial diagnosis, or recurrent disease more than 6 months after surgery or adjuvant therapy. 

The prespecified interim analysis was conducted after a median 16.8 months for the 341 patients who were randomly assigned to receive durvalumab 1500 mg every 3 weeks alongside up to eight cycles of gemcitabine plus cisplatin, and after a median 15.9 months of follow-up for the 344 patients instead given placebo plus chemotherapy. At this time, a corresponding 18.6% and 5.8% of patients were continuing treatment. 

Median OS was significantly longer for the patients given the PD-L1 inhibitor plus chemotherapy than the controls, at a median 12.8 versus 11.5 months and a hazard ratio (HR) for death of 0.80. The study’s design means that these results should “be considered the final, formal statistical analysis for overall survival”, the presenter explained. 

Do-Youn Oh observed that the OS curves separated after around 6 months of follow-up, so that the HR for OS was a nonsignificant 0.91 for the first 6 months and a significant 0.74 thereafter. And the difference between the OS rates of the durvalumab and placebo arms increased between 12 months of follow-up (54.1 vs 48.0%) and 24 months (24.9 vs 10.4%). 

OS favoured durvalumab use across subgroups of patient age, sex, race, region, ECOG performance status, primary tumour location, resection status and stage, and PD-L1 expression, she said. 

The secondary endpoint of median progression-free survival was also significantly longer for the durvalumab-treated patients than controls, at 7.2 versus 5.7 months and a HR for progression or death of 0.75 in favour of the PD-L1 inhibitor. 

The presenter noted that the difference in the PFS rates between the arms favouring durvalumab over placebo was consistent at 6 months (58.3 vs 47.2%), 9 months (34.8 vs 24.6%) and 12 months (16.0 vs 6.6%). 

Furthermore, the objective response rate was significantly higher for the durvalumab than the placebo group (26.7 vs 18.7%, HR=1.60), with complete responses reported in 2.1% and 0.6% of the groups, respectively. Patients given durvalumab plus chemotherapy were faster to respond to treatment than controls (median 1.6 vs 2.7 months) and had a longer duration of response than controls (median 6.4 vs 6.2 months). 

Do-Youn Oh highlighted that after 9 months of follow-up, 32.6% of durvalumab-treated patients continued to respond to treatment versus 25.3% of their placebo-treated counterparts and the difference extended between the groups after 12 months, when 26.1% and 15.0% of patients, respectively, continued to be in response. 

Turning to the safety analysis, the presenter reported that the median duration of treatment in the two groups was similar for durvalumab/placebo (7.33 vs 5.77 months), gemcitabine (5.19 vs 5.03 months) and cisplatin (5.13 vs 4.88 months).  

“Durvalumab did not add additional toxicity to that observed with [gemcitabine plus cisplatin] and no new safety signals were identified from the known safety profiles of each individual treatment”, she said. 

The durvalumab and placebo arms experienced similar rates of any-grade treatment-related adverse events (TRAEs; 92.9 vs 90.1%), grade 3–4 TRAEs (62.7 vs 64.9%) and serious TRAEs (15.7 vs 17.3%), as well as rates of discontinuation for TRAEs (8.9 vs 11.4%) and fatal TRAEs (0.6 vs 0.3%). 

The most common grade 3–4 TRAEs were haematological toxicities and rates of these were comparable between the durvalumab and placebo arms, most commonly neutrophil decreases (20.7 vs 25.4%), neutropenia (19.2 vs 20.2%) and anaemia (18.9 vs 18.7%). 

Any-grade immune-mediated AEs occurred in 12.7% of the durvalumab arm and 4.7% of the control arm but the presenter emphasized that grade 3–5 immune-mediated AEs were “quite rarely observed even with durvalumab”, affecting just 2.4% and 1.5% of patients, respectively. 

“TOPAZ-1 is the first global phase 3 trial to report positive results testing immunotherapy plus chemotherapy as first-line treatment for advanced [biliary tract cancer]”, the investigator concluded. 

Noting that the OS curves appear to separate at 6 months after chemotherapy discontinuation, Nilofer Azad questioned whether the survival benefits of durvalumab come from its use as first-line treatment or as a maintenance therapy. 

She added that further analysis was required to determine the patients who will benefit most from the addition of durvalumab, such as its use in Asian versus non-Asian patients, and those with viral hepatitis, liver fluke disease and other comorbidities. 


Oh D-Y, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol 2022;40(4_suppl):378–378. DOI: 10.1200/JCO.2022.40.4_suppl.378

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

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