Durvalumab, gemcitabine and cisplatin continue to show clinically meaningful long-term survival in biliary tract cancer patients

Dr Do-Youn Oh - Seoul National University Hospital, Seoul, Korea

This year at the ESMO Gastrointestinal Cancer Congress we presented three-year survival rate of the TOPAZ-1 study in biliary tract cancer. In the TOPAZ-1 study, the primary analysis, which was done at 2021, demonstrated that durvalumab plus gemcitabine/cisplatin significantly improved overall survival compared to placebo plus gemcitabine/cisplatin. At that time, OS hazard ratio was 0.80 and with an acceptable safety profile. With that, durvalumab plus gemcitabine/cisplatin became a new standard of care for first-line advanced biliary tract cancer patients. This year we presented updated survival at a median follow-up of 41 months. Actually, this median follow-up of 41 months is the longest dataset in this field. The data cut-off was done at October 2023, which was around three years after the last patient was randomised. With this updated follow-up, the OS benefit with durvalumab plus gemcitabine/cisplatin has been continued. Now, the OS hazard ratio is 0.74, which is numerically improved from 0.80 of the primary analysis of TOPAZ-1 study. Now I say that the TOPAZ-1 OS hazard ratio is 0.74 and the three-year overall survival rate is 14.6% in the durvalumab arm and 6.9% in the placebo arm. The three-year survival rate was more than doubled by adding durvalumab on top of gemcitabine/cisplatin.

Interestingly, when you look at this three-year overall survival rate by the patients’ best objective response, especially in patients who achieved a CR/PR response, there is a responder, their three-year OS rate was 31.9% in the durvalumab arm, a very good number, and 15.6% in the placebo arm, so more than doubled. When you look at the stable disease patients, again, the three-year survival rate was 9.8% in the durvalumab arm and 5.1% in the placebo arm. The three-year survival rate was doubled. So, when we combine CR, PR, and stable disease all together, so the patients who achieved disease control, their median overall survival was 14.6 months, surely longer than the 12.9 months of the FAS population, and their three-year overall survival rate was 17% in the durvalumab arm and 7.6% in the placebo arm.

In this analysis, we also did a very interesting analysis focusing on extended long-term survival. With that, we defined this long-term survival as the patients who were still alive more than 30 months after randomisation. We looked into their baseline characteristics, and we found that generally these long-term survivors’ baseline characteristics were generally quite consistent with the FAS population. All clinically relevant subgroups were presented in this long-term survival group, including primary tumour location – gallbladder, or intrahepatic, extrahepatic, cholangiocarcinoma, all – and  also region, Asia versus non-Asia, and also PD-L1 expression, so high PD-L1 or low or negative PD-L1 population. It means that no single subgroup drove the long-term survivorship. In the durvalumab arm, 17% of patients belonged to this long-term survival. It means when we treat the patients with gemcitabine/cisplatin plus durvalumab, 17% of patients can live longer than 30 months. However, in the placebo arm 8.7% of patients belong to this long-term survival.

What about the safety update? There were no meaningful changes in SAE and tumour-related SAE from previous analyses. In this long-term follow-up dataset, the median treatment duration of durvalumab was 7.3 months. When you look at the long-term survivors, their median treatment duration of durvalumab was 17.8 months, quite a long duration of treatment. Despite a longer duration of exposure of durvalumab, the long-term survival group’s SAE were quite comparable between arms, and even less frequent than the patients in the FAS population. So, these updated survival and safety data of the TOPAZ-1 study further support use of durvalumab plus gemcitabine/cisplatin as a standard of care for first-line advanced biliary tract cancer. After a median follow-up of 41 months, durvalumab plus gemcitabine/cisplatin continued to demonstrate a clinically meaningful really long-term survival benefit.

What is the clinical significance of these results?

So already, durvalumab plus gemcitabine/cisplatin is the current standard of care. With this long-term follow-up dataset, we can find a really long-term survival benefit with this regimen in this population. Before these phase III studies it was quite uncommon for us to mention about three-year survival rate in this biliary tract cancer field. But now, we clearly say that by treating patients using durvalumab plus a gemcitabine/cisplatin combination, the three-year survival rate is 14.6%. Very interesting data, and very important data in this field.