Wei-Sen Lam

Purpose:Anti–PD-1/PD-L1 blockade combined with chemotherapy has become the first-line treatment for advanced biliary tract cancers. Combined anti–PD-1/CTLA-4 blockade using nivolumab and ipilimumab has shown encouraging activity in patients with intrahepatic cholangiocarcinoma (iCCA) and gallbladder carcinoma (GBC) in two trials (CA209–538 and SWOG1609). MoST-CIRCUIT further evaluated combined checkpoint blockade using nivolumab/ipilimumab in patients with advanced iCCA and GBC. Patients and Methods:Patients with a maximum of 1 line of prior systemic therapy were enrolled as cohort B into MoST-CIRCUIT, a single-arm, nonrandomized phase 2 trial. Patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks for 96 weeks. Response (RECIST 1.1) was assessed every 12 weeks. Coprimary endpoints were objective response rate (ORR) and 6-month progression-free survival (6-PFS), with the secondary endpoints being median overall survival (mOS), PFS, and treatment-related toxicity. Results:Sixty patients (37 iCCA and 23 GBC) were enrolled; 85% were pretreated, including 13 patients with durvalumab. The ORR was 12% (2% complete response, 10% partial response): 3% and 26% in the iCCA and GBC subgroups, respectively. The 6-PFS was 27% (iCCA 19%; GBC 39%), and mOS was 7 months. In the immunotherapy-naïve population, the ORR was 19% (iCCA 10%; GBC 38%). Severe immune-related adverse events were observed in 20% of patients. Conclusions:Efficacy was limited in what is the largest biliary tract cancer cohort treated to date with combined anti–CTLA-4/PD-1 blockade. Encouraging activity was observed in the GBC subgroup. Further evaluation of checkpoint inhibition in biliary tract cancer should focus on patients with GBC.

Representativeness of the Study population.

Purpose: Anti–PD-1/PD-L1 blockade combined with chemotherapy has become the first-line treatment for advanced biliary tract cancers. Combined anti–PD-1/CTLA-4 blockade using nivolumab and ipilimumab has shown encouraging activity in patients with intrahepatic cholangiocarcinoma (iCCA) and gallbladder carcinoma (GBC) in two trials (CA209–538 and SWOG1609). MoST-CIRCUIT further evaluated combined checkpoint blockade using nivolumab/ipilimumab in patients with advanced iCCA and GBC. Patients and Methods: Patients with a maximum of 1 line of prior systemic therapy were enrolled as cohort B into MoST-CIRCUIT, a single-arm, nonrandomized phase 2 trial. Patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks for 96 weeks. Response (RECIST 1.1) was assessed every 12 weeks. Coprimary endpoints were objective response rate (ORR) and 6-month progression-free survival (6-PFS), with the secondary endpoints being median overall survival (mOS), PFS, and treatment-related toxicity. Results: Sixty patients (37 iCCA and 23 GBC) were enrolled; 85% were pretreated, including 13 patients with durvalumab. The ORR was 12% (2% complete response, 10% partial response): 3% and 26% in the iCCA and GBC subgroups, respectively. The 6-PFS was 27% (iCCA 19%; GBC 39%), and mOS was 7 months. In the immunotherapy-naïve population, the ORR was 19% (iCCA 10%; GBC 38%). Severe immune-related adverse events were observed in 20% of patients. Conclusions: Efficacy was limited in what is the largest biliary tract cancer cohort treated to date with combined anti–CTLA-4/PD-1 blockade. Encouraging activity was observed in the GBC subgroup. Further evaluation of checkpoint inhibition in biliary tract cancer should focus on patients with GBC.

Background Prescription-related errors and misinterpretation of oral cancer treatment instructions can lead to significant harm or fatal outcomes for patients. The impact of specialist pharmacist-led consultation for patients taking oral antineoplastic medicines (OAMs) across a range of cancer types in an Australian setting has not been studied. Aim To evaluate the impact of specialist cancer pharmacist patient consultation in a pharmacist-led anticancer clinic across a range of cancer types and evaluate health service staff perceptions of these consultations. Method Retrospective data were collected from electronic patient medical records from 2017 to 2020 at a Western Australian quaternary hospital. The impacts of pharmacist clinical interventions were classified using a validated tool and specialist interdisciplinary panel consensus. An online staff survey was conducted using Qualtrics. Results Of 246 patients reviewed, 76 (30.8%, p < .001) had received a clinical intervention of which 48 (63.2%) were classified as high-extreme and 28 (36.8%) as low-moderate impact (p = .021). Patients on >= 5 concurrent medications or > 65 years may represent high risk groups. Thirty-seven clinical staff were surveyed (37/55; 67.3%) and all strongly agreed/ agreed pharmacist consultation improved patient understanding and medication management confidence (p < .001). All cancer center staff (26/26) strongly agreed/agreed the clinic added value to the cancer service (p < .001), and 96.2% perceived it improved patient outcomes (p < .001). Conclusions Specialist pharmacist-led patient consultation for patients on OAM regimens may protect patients from high and extreme risk of harm. Specialist interdisciplinary staff supported this service.