Patient-reported outcomes for the phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer.

Abstract

4070 Background: TOPAZ-1 (NCT03875235) is a randomized, double-blind, global, Phase 3 study evaluating the efficacy and safety of durvalumab (D) in combination with (+) gemcitabine and cisplatin (GC) as first-line treatment for patients (pts) with advanced biliary tract cancer (BTC).1 D + GC significantly improved overall survival (OS) versus placebo (PBO) + GC and represents a new treatment option. Methods: A pre-planned secondary objective of TOPAZ-1 was to assess pt-reported outcomes (PROs) for pts receiving D + GC versus PBO + GC. Pts with BTC were randomized 1:1 to D (1500 mg) or PBO, + G (1000 mg/m2) and C (25 mg/m2), for up to 8 cycles, followed by D or PBO monotherapy until disease progression, unacceptable toxicity, or other discontinuation criteria were met. PROs were assessed with the European Organisation for Research and Treatment of Cancer 30-item Quality of Life (QoL) Questionnaire, EORTC QLQ-C30 (C30), and the BTC 21-item module, EORTC QLQ-BIL21 (BIL21). Time to deterioration (TTD) was the primary assessment of PROs; defined as the time from randomization to the date of the first pre-specified, clinically meaningful deterioration (e.g. disease progression). The PRO analysis set included all pts from the full analysis set who completed a questionnaire. Results: Compliance rates for PROs were high at baseline (>81%) and remained high (majority >70% over 28 cycles) for both treatment groups. Baseline scores were comparable between treatment groups. Addition of D was well tolerated, with no significant difference in TTD in D + GC versus PBO + GC for pt-reported symptoms or functioning using either C30 or BIL21 (Table), or Global Health Status/QoL (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.69–1.12; p=0.279). Conclusions: Addition of D to GC improved OS (Oh D-Y, et al. J Clin Oncol 2022;40(suppl 4). Abs 378) and was well tolerated with no difference in TTD of QoL for pts, supporting D + GC as a new treatment option for pts with BTC. Clinical trial information: NCT03875235. [Table: see text]

Immunotherapy for the treatment of biliary tract cancer: an evolving landscape

“…Quality of life (QOL) was similar for both arms, as well. 91 Results of the safety analysis were consistent with prior studies and similar between treatment groups, and give comfort to treating with the IO and chemotherapy TOPAZ-1 regimen in terms of tolerability.…”

Evaluating the Therapeutic Potential of Durvalumab in Adults with Locally Advanced or Metastatic Biliary Tract Cancer: Evidence to Date

“…Additionally, a subsequent analysis of the TOPAZ-1 trial analyzed time to deterioration via patient reported outcomes using multiple quality-of-life questionnaires. 30 The study found that the addition of durvalumab to gemcitabine plus cisplatin did not result in a significant difference in time to deterioration with regards to patient quality-of-life or function. Overall, this demonstrates that the addition of durvalumab was well tolerated.…”

Recent Advances in Systemic Therapy for Advanced Intrahepatic Cholangiocarcinoma

“…Immune-mediated adverse event was found in 12.7% of patients who received additional durvalumab, including 2.4% of patients with grade 3–4 event, and 0.9% of patients discontinuing the treatment due to adverse events [ 88 ]. In the quality-of-life investigation, there was no difference between the GemCis group and durvalumab plus GemCis group [ 89 ]. From the exploratory analysis, the efficacy and safety outcomes were similar across different regions (Asia vs. others) and primary tumor location (IHCCA vs. EHCCA vs. GBCA) [ 90 , 91 ].…”