Results of the randomized, double-blind, global, phase 3 TOPAZ-1 trial (NCT03875235) demonstrated that the first-line chemoimmunotherapy regimen of the PD-L1 inhibitor durvalumab plus gemcitabine/cisplatin (GemCis; median follow-up, 13.7 months) significantly improved overall survival (OS) versus placebo plus GemCis (median follow-up, 12.6 months).1 Given that primary biliary tract cancer (BTC) tumor location may impact prognosis and response to treatment, an exploratory subgroup analysis of TOPAZ-1 was conducted to assess efficacy outcomes by primary tumor location (intrahepatic cholangiocarcinoma [iCCA], extrahepatic cholangiocarcinoma [eCCA], or gallbladder cancer [GBC]) in patients receiving durvalumab versus placebo. These results were presented at the 2022 ESMO GI congress.
Eligible patients with BTC were randomly assigned 1:1 to receive durvalumab (1500 mg) or placebo on day 1 every 3 weeks plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) on days 1 and 8 every 3 weeks for up to 8 cycles, followed by durvalumab or placebo monotherapy until disease progression, unacceptable toxicity, or discontinuation. Stratification was by disease status (initially unresectable vs recurrent) and primary tumor location (iCCA vs eCCA vs GBC). Efficacy outcomes assessed included OS, progression-free survival (PFS), objective response rate (ORR), and duration of response per RECIST version 1.1.
Patient numbers were balanced between the durvalumab and placebo arms for iCCA (190 and 193 patients, respectively), eCCA (66 and 65 patients, respectively), and GBC (85 and 86 patients, respectively), as were age, sex, and geographic region. Most patients with iCCA or GBC presented with initially unresectable disease at baseline.
Across all primary tumor locations, OS hazard ratio (HR) favored durvalumab compared with placebo: 0.76 for iCCA, 0.76 for eCCA, and 0.94 for GBC. Regional analysis showed that OS benefit was consistent across regions for GBC, with greater benefit for eCCA in Asia. Similarly, PFS HR significantly favored durvalumab versus placebo across primary tumor locations (iCCA, 0.79; eCCA, 0.52; GBC, 0.90). ORR favored durvalumab versus placebo for iCCA (24.7% vs 15.5%; odds ratio [OR], 1.79), eCCA (28.8% vs 15.6%; OR, 2.18), and GBC (29.4% vs 27.9%; OR, 1.08). The ORR benefit was consistent and durable across primary tumor locations. The use of subsequent anticancer therapy across all primary tumor locations was lower in patients receiving durvalumab plus GemCis versus placebo plus GemCis.
The incidence of grade 3 or 4 adverse events or grade 3 or 4 treatment-related adverse events was generally comparable among treatment groups, irrespective of primary tumor location.
Based on the results of the TOPAZ-1 study subgroup analysis by primary tumor location, the authors concluded that “the addition of durvalumab to GemCis appeared to improve efficacy outcomes for patients with iCCA, eCCA, and GBC. Though the magnitude of efficacy improvement varied slightly between primary tumor locations, the benefit of durvalumab was observed consistently. These findings support durvalumab plus GemCis as a treatment option for BTC, irrespective of primary tumor location.”
Reference
- 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):378-378.
Source: He AR, Valle JW, Lee C-K, et al. Outcomes by primary tumor location in patients with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study. European Society for Medical Oncology World Congress on Gastrointestinal Cancer 2022. Abstract O-1.