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]
436 Background: The phase 2 Study 22 trial (NCT02519348) investigated durvalumab (anti-programmed cell death ligand-1 [PD-L1] antibody) and tremelimumab (anti-cytotoxic T-lymphocyte associated antigen 4 antibody) as monotherapy, or durvalumab in combination with tremelimumab or bevacizumab (anti-vascular endothelial growth factor [VEGF] antibody), for the treatment of patients with unresectable hepatocellular carcinoma (uHCC). Results of Study 22 that evaluated durvalumab and tremelimumab as monotherapy or in combination were reported previously. PD-L1 inhibition plus VEGF inhibition with bevacizumab may exhibit an additive effect to improve clinical activity. Herein, we report results from a single-arm cohort of Study 22, evaluating durvalumab plus bevacizumab as first-line treatment in patients with uHCC. Methods: Patients with uHCC who had not received any prior systemic therapy were administered durvalumab 1120 mg plus bevacizumab 15 mg/kg once every 3 weeks. Adequate endoscopic therapy according to institutional standards was required for patients with a history of gastrointestinal bleeding for >12 months or those at high risk for esophageal varices. The primary endpoint was safety. Secondary endpoints included confirmed objective response rate (ORR; assessed by blinded independent central review [BICR] according to RECIST v1.1), duration of response (DoR; RECIST v1.1 by BICR) and overall survival (OS). Results: At the data cut-off (November 6, 2020), 47 patients were allocated to receive treatment. Median total treatment duration was 6.2 months (durvalumab) and 4.1 months (bevacizumab). Thirty-three (70.2%) patients experienced an adverse event possibly related to treatment (TRAE). Grade 3 or 4 TRAEs occurred in 4 (8.5%) patients; serious TRAEs occurred in 5 (10.6%) patients, including gastric ulcer perforation, ascites, and liver tumor rupture, possibly related to bevacizumab, and raised creatinine and pneumonitis, possibly related to durvalumab. There were 3 (6.4%) discontinuations and no deaths associated with TRAEs. Objective responses (RECIST 1.1 by BICR) were confirmed in 10 patients (ORR, 21.3%; 95% CI, 10.7–35.7); median DoR (RECIST 1.1 by BICR) was not reached. Median OS was not reached (95% CI, 12.52 months–non-estimable). Conclusions: Durvalumab plus bevacizumab was well tolerated and showed promising clinical activity in patients with uHCC. Durvalumab with or without bevacizumab in combination with transarterial chemoembolization is being investigated as locoregional therapy in patients with HCC not amenable to curative treatment in the phase 3 EMERALD-1 study (NCT03778957), and durvalumab with or without bevacizumab is being investigated in patients with HCC at high risk of recurrence after curative treatment in the phase 3 EMERALD-2 study (NCT03847428). Clinical trial information: NCT02519348.
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