TOPAZ-1 Study Explores Potential Prognostic Factors of Overall Survival for Patients With Advanced Biliary Tract Cancer

Aiwu Ruth He, MD, PhD, Georgetown University Hospital, Washington, DC, and colleagues presented their study “Potentially prognostic factors of overall survival in advanced biliary tract cancer in the randomised phase III TOPAZ-1 study” at the 2023 ESMO Congress. In this interview with the Journal of Clinical Pathways, Dr He summarizes the study and discusses treatment approaches for patients with biliary tract cancer.

Transcript:

Aiwu Ruth He: I'm Aiwu Ruth He, a GI medical oncologist working at Georgetown University Hospital in Washington, DC.

Could you please briefly summarize the TOPAZ-1 study?

Dr He: The TOPAZ-1 study is a randomized, double-blinded, global study that compares the combination of durvalumab plus gemcitabine and cisplatin (GemCis). With GemCis treatment, close to 700 patients with locally advanced or metastatic biliary tract cancer were (BTC) enrolled in this study. The primary endpoint of the study is overall survival. The study is stratified for disease status, initially unresectable or recurrent disease, and primary tumor location, such as intrahepatic cholangio, extrahepatic cholangio, vs gallbladder cancer.

How effective do you think durvalumab in combination with GemCis is compared to the current treatment options available for advanced biliary tract cancer?

Dr He: Durvalumab plus GemCis improved overall survival vs placebo plus GemCis with an updated hazard ratio of 0.76 after longer follow-up time. And if we look at landmark survival analysis, there is an improvement of landmark survival rate at 24 months to 25% with the combination of durvalumab GemCis from 10% with the combination of placebo plus GemCis.

Which prognostic factors identified in the study might be most pertinent for designing a treatment plan for patients with advanced biliary tract cancer and why?

Dr He: In this study presented at ESMO, we assessed the baseline characteristics for potential prognostic or predictive value in the TOPAZ-1 study. And from literature review, here are the baseline clinical factors that have shown to be prognostic, and we've evaluated those prognostic factors in patients enrolled in the TOPAZ-1 study. And I'm going to list all the clinical factors that have been evaluated, such as neutrophil lymphocyte ratio, CA99, and disease status, ECOG performance status, disease classification, CEA, liver metastasis or liver involvement, and LDH, albumin, and transaminases. And consistent with the literature, all these prognostic factors have shown to be prognostic in patients enrolled in the TOPAZ-1 study.

Then we did a stepwise selection of the prognostic factors to adjust for hazard ratio after adjusting all these prognostic factors. The adjusted hazard ratio was 0.70 compared to 0.76 based on the adjustment for the stratification factors, suggesting that there's a consistency in the improvement of overall survival after we have adjusted all the prognostic factors. From this study, I think we want to indicate that when we look at the primary outcome of a study, it is important to factor in the prognostic factors because those may affect patients’ outcomes on treatment.

Then we looked at these clinical factors to see if they are predictors. And we found no predictor factors for durvalumab plus GemCis vs placebo plus GemCis was identified. So based on the current analysis from all the clinical factors, we have not identified any predictor that would select in or out of the combination treatment.

How might the TOPAZ-1 study alter the first-line treatment approach for patients diagnosed with advanced biliary tract cancer?

Dr He: 10 years ago, the global phase 3 study ABC-02 established GemCis as the first-line treatment for advanced BTC. 10 years later, based on the results from the TOPAZ-1 study, durvalumab plus GemCis has been approved for the treatment of patients with advanced biliary tract cancer by the US FDA and the European Medicine Agency and in many other countries. Now it's used as a standard of care, first-line systemic therapy for advanced biliary tract cancer.