Ryan Haumschild, PharmD, MS, MBA, CPEL

Panelists discuss how common barriers to implementing trifluridine/tipiracil plus bevacizumab combination therapy include complex pill burden management with multiple bottle strengths that can confuse patients during dose reductions, procedural complications requiring bevacizumab holds that patients sometimes fail to disclose in advance, and hypertension management challenges that create patient anxiety about treatment delays, while emphasizing that adherence support strategies include close monitoring with biweekly visits, written dosing calendars, alternative five-day dosing schedules aligned with infusion timing, and incorporating patient-reported outcomes into shared decision-making to optimize treatment success despite these practical barriers.

Panelists discuss how real-world dose adjustment decisions in metastatic colorectal cancer are primarily driven by individual patient factors rather than package insert recommendations, emphasizing the importance of understanding each patient's goals, values, comorbidities, and tolerance thresholds through collaborative multidisciplinary decision-making, since patients frequently ask "how will this make me feel?" and often prioritize quality of life over strict adherence to standard dosing, with the key insight that dose reductions can maximize efficacy by keeping patients on therapy longer rather than causing treatment discontinuation from intolerable toxicities.

Panelists discuss how managing common toxicities in combination therapies requires specific strategies including dose reductions and growth factor support for neutropenia with trifluridine/tipiracil, antihypertensive management for blood pressure elevations across different agents, and careful patient selection considering contraindications such as previous pelvic radiation (GI perforation risk), cardiac conditions, anticoagulation therapy (hemorrhage risk), hepatic impairment, advanced age, and complex pill burden management, emphasizing the importance of multidisciplinary care and selecting conscientious patients capable of adhering to precise dosing requirements.

Panelists discuss how the SUNLIGHT trial's demonstration that adding bevacizumab to trifluridine/tipiracil improves overall survival and progression-free survival represents the best available data in refractory colorectal cancer, with quality of life findings showing longer time to definitive deterioration being particularly significant for patient counseling since patients in third-line and beyond settings prioritize both survival benefit and maintaining good quality of life, making this combination compelling as it provides efficacy improvement without dramatically compromising patient well-being.

Panelists discuss how third-line metastatic colorectal cancer treatment has evolved from limited options like FOLFOX and FOLFIRI to multiple available agents including regorafenib, trifluridine/tipiracil, trifluridine/tipiracil plus bevacizumab, and fruquintinib, emphasizing the importance of comprehensive biomarker testing to identify rare fusions and actionable targets before selecting among these therapies, each with distinct mechanisms of action and tolerability profiles that require careful sequencing and adherence management to optimize clinical outcomes.

Panelists discuss how recent FDA regulatory actions regarding obeticholic acid have raised concerns about its long-term safety profile and accessibility, leading health care teams to develop strategies for supporting patients through treatment transitions while navigating insurance coverage and access challenges for newer primary biliary cholangitis (PBC) therapies.

Panelists discuss how transitioning patients from obeticholic acid to seladelpar or elafibranor requires close monitoring of liver biochemistry, pruritus severity, medication adverse effects, and quality of life measures while providing clear patient education about expected timeline for symptom improvement and potential adjustment periods.

Panelists discuss how clinicians may transition patients to newer agents due to factors such as inadequate biochemical response, tolerability issues (particularly pruritus), or patient preference, while carefully considering the need for washout periods based on each drug's pharmacokinetics and mechanism of action.

Panelists discuss how long-term safety monitoring for second-line primary biliary cholangitis (PBC) therapies requires systematic assessment of liver function, lipid profiles, and potential drug-specific adverse effects while emerging 5-year safety data for seladelpar continues to demonstrate a favorable risk profile compared with other treatment options.

Panelists discuss how the safety profiles of second-line primary biliary cholangitis (PBC) therapies in compensated cirrhosis show varying levels of risk, with recent abstracts from EASL and AASLD 2024.

Panelists discuss how managing primary biliary cholangitis (PBC) in women of childbearing age requires careful consideration of pregnancy risk categories for different medications, with UDCA being the safest option during pregnancy, while second-line therapies require strict contraception and careful monitoring of hormone interactions to ensure optimal safety and efficacy.

Panelists discuss how hepatotoxicity risks vary among second-line primary biliary cholangitis (PBC) treatments, with seladelpar and elafibranor showing favorable hepatic safety profiles compared to obeticholic acid, though all require regular liver function monitoring and dose adjustments based on individual patient response and disease severity.

Panelists discuss how safety considerations for primary biliary cholangitis (PBC) treatment include monitoring liver function tests, managing pruritus and fatigue, assessing drug interactions, and evaluating individual patient factors like pregnancy status and comorbidities, which all influence the choice between ursodeoxycholic acid and second-line therapies.

Panelists discuss how sustained treatment success in primary biliary cholangitis (PBC) requires regular monitoring of biochemical response markers, assessing patient adherence, managing potential adverse effects, and making timely adjustments to treatment strategies based on individual patient responses to seladelpar and elafibranor.

Panelists discuss how seladelpar showed remarkable efficacy in the RESPONSE trial, demonstrating significant improvements in alkaline phosphatase levels and other biochemical markers compared with placebo.

Panelists discuss how elafibranor demonstrated significant efficacy in the ELATIVE trial, which strengthens confidence in its role as a long-term treatment option for patients with primary biliary cholangitis (PBC) who inadequately respond to ursodeoxycholic acid.

Panelists discuss how some patients with primary biliary cholangitis (PBC) have an inadequate response to ursodeoxycholic acid and require second-line treatments, with options including obeticholic acid, seladelpar, and elafibranor, which improve bile acid homeostasis and reduce inflammation.

Panelists discuss how the main treatment goals for patients with primary biliary cholangitis (PBC) include improving liver biochemistry, preventing disease progression to cirrhosis, managing symptoms, and enhancing overall quality of life through regular monitoring and appropriate therapeutic interventions.

Panelists discuss how ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis (PBC), with early initiation being crucial for optimal outcomes and prevention of disease progression.

Panelists discuss how primary biliary cholangitis (PBC) often presents asymptomatically but can be diagnosed through elevated alkaline phosphatase levels, positive antimitochondrial antibodies, and liver biopsy when necessary.