Summary: monitoring and supportive care relevant to tovecimig plus paclitaxel

Three strands of care management apply. First, molecular profiling determines whether a participant belongs to the biomarker-directed pathway or to the chemotherapy pathway that tovecimig targets; guidelines recommend profiling when first-line systemic treatment is initiated, and COMPANION-002 excluded participants eligible for a labelled targeted regimen. Second, biliary tract cancer requires ongoing biliary and infection management independent of systemic therapy: guidelines recommend biliary drainage with percutaneous transhepatic drainage when endoscopic access is not possible, prompt treatment of sepsis secondary to biliary obstruction, patient education on stent patency and on the signs of obstruction or infection, and follow-up every 8 to 12 weeks with computed tomography or magnetic resonance imaging supplemented by carbohydrate antigen 19-9 or carcinoembryonic antigen when secreted. COMPANION-002 required adequate biliary excretion at entry and excluded participants with percutaneous transhepatic biliary drains.

Third, the adverse event profile of tovecimig plus paclitaxel defines the monitoring program. The most common treatment-emergent adverse events in the combination arm were hypertension (69%) and fatigue (67%), and the most common related grade 3 or higher events were hypertension (44%) and neutropenia (36%), which indicates a need for blood pressure measurement at every visit with antihypertensive management, and for complete blood counts before each weekly paclitaxel dose. The angiogenesis-directed mechanism is reflected in the trial's entry requirements and exclusions, which covered urine protein by dipstick with 24-hour confirmation, uncontrolled hypertension, hemorrhage-related and gastroenterological disease, and current or recent therapeutic anticoagulation or antiplatelet use, so proteinuria, bleeding risk, and concomitant anticoagulation require assessment before and during treatment. In the earlier phase 2 study of the same combination the most frequent grade 3 or higher events were neutropenia (50.0%), hypertension (16.7%), anemia (12.5%), and thrombocytopenia (8.3%).

Molecular profiling to assign the treatment pathway

“Molecular profiling is recommended when first-line systemic treatment is initiated in patients with locally advanced, advanced or metastatic disease, particularly in those at high risk of progression or recurrence [I, A].” (opens the source at this quote in a new tab)

Follow-up interval and tumor marker monitoring during systemic therapy

“During systemic and locoregional therapy for advanced disease, follow-up should be conducted at a frequency of 8-12 weeks. In addition to imaging with CT or MRI, CA 19-9 or CEA levels may be used to monitor the course of the disease if one or both are known to be secreted [IV, A]” (opens the source at this quote in a new tab)

Biliary drainage, infection management, and patient education

“In patients with biliary obstruction, biliary drainage and subsequent treatment should be carried out; when endoscopic access is not possible, percutaneous transhepatic drainage is recommended [IV, A]” (opens the source at this quote in a new tab)
“Sepsis secondary to biliary obstruction is common and should be treated promptly [IV, A]” (opens the source at this quote in a new tab)
“Patients should be advised of the likely duration of stent patency and of symptoms and signs which are indicative of biliary obstruction or infection [V, A]” (opens the source at this quote in a new tab)

Adverse events requiring monitoring with tovecimig plus paclitaxel

“Tovecimig was generally well tolerated and the safety profile was consistent with previously reported data from prior studies, with no new safety signals. The most commonly reported treatment emergent adverse events in the tovecimig combination arm were hypertension (69%) and fatigue (67%). The most common related treatment-emergent adverse events of Grade 3 or higher included hypertension (44%) and neutropenia (36%).” (opens the source at this quote in a new tab)

“The most frequent TEAEs of grade 3 or higher were neutropenia (50.0%), hypertension (16.7%), anemia (12.5%) and thrombocytopenia (8.3%)” (opens the source at this quote in a new tab)

Baseline assessments and exclusions relevant to angiogenesis blockade

Field	Registry record
Inclusion criterion, biliary excretion	“No evidence of ongoing infection and adequate biliary excretion or patients whose adequate biliary excretion can be confirmed with the following procedures:”
Inclusion criterion, proteinuria	“Urine protein ≤ 1+ by Dipstick”
Exclusion criterion, biliary drains	“Patients with percutaneous transhepatic biliary drains (PTBD)”
Exclusion criterion, targeted therapy eligibility	“Patients who are eligible to be treated with a molecularly targeted therapy on a labelled regimen after receiving first-line chemotherapy.”

Tovecimig (CTX-009)

Care management intervention strategies