Lenvatinib for RAI-Refractory DTC: A Multidisciplinary View with Dr. Newbold

Introduction to the Journal Club

Welcome and Overview

• The session welcomes participants from around the world, expressing gratitude for their attendance and wishing them happy holidays.

• The focus of today's journal club is on advanced thyroid oncology, specifically discussing an article about lenvatinib for treating radioiodine refractory differentiated thyroid cancer.

Introduction of Speakers

Expert Panel

• Dr. Kate Newald is introduced as a consultant clinical oncologist specializing in thyroid and head/neck cancers at the Royal Marsden Hospital, London. She has expertise in various therapies including systemic therapy and molecular profiling of thyroid cancer.

• Dr. Alan Ho from Memorial Sloan Kettering is also introduced; he specializes in translational research related to thyroid cancer and leads several oncology initiatives.

Presentation by Dr. Kate Newald

Background on Lenvatinib Use

• Dr. Newald discusses a collaborative effort led by experts to compile experiences managing iodine refractory patients with advanced disease using lenvatinib, highlighting its significance nearly ten years after the original SELECT trial findings.

• The presentation aims to guide clinicians on patient selection, treatment initiation timing, monitoring strategies, and adverse event management when using lenvatinib for these patients.

Understanding Thyroid Cancer Progression

Disease Characteristics

• Most thyroid cancers present early and respond well to standard treatments; however, local recurrence occurs in about 20% of cases with distant metastases affecting 10-15%.

• A third of advanced differentiated thyroid cancers lose iodine uptake ability, significantly impacting survival rates—those retaining sensitivity can have over 60% ten-year survival rates compared to only 10% for those that do not retain it.

Defining Radioiodine Refractory Thyroid Cancer

Criteria for Diagnosis

• Radioiodine refractory status includes disease that does not take up radioactive iodine post-treatment or shows progression despite initial uptake during earlier treatments. This may involve mixed responses where some lesions still uptake iodine but progress nonetheless.

• FDG-PET CT scans are recommended to assess disease activity alongside traditional imaging methods when determining treatment efficacy with radioactive iodine therapy.

Treatment Approaches Post-Refractoriness

Palliative Care Focus

• Once defined as iodine refractory, treatment shifts towards palliative care aimed at prolonging progression-free survival while improving quality of life through symptom management rather than curative intent. Multikinase inhibitors like lenvatinib are among available options but come with significant side effects such as hypertension and fatigue that need careful management before initiating therapy.

Molecular Profiling Considerations

Targeted Therapies

• Patients should undergo molecular profiling upon becoming iodine refractory to identify specific alterations amenable to targeted therapies; drugs targeting RET fusions are highlighted as particularly effective options available in different regions (e.g., selpercatinib).

Efficacy of Multikinase Inhibitors

Limitations and Side Effects

• While multikinase inhibitors like lenvatinib have changed the natural history of iodine refractory thyroid cancer positively, they do not cure the disease but slow its progression temporarily before resistance develops; thus careful risk-benefit assessments are crucial prior to starting treatment due to potential adverse events associated with long-term use.(684)

Expert Consensus Development

Guidelines Creation

• A group of European specialists convened virtually aiming to create practical guidance on managing patients planned for lenvatinib therapy focusing on aspects such as baseline workup, symptom relevance, multidisciplinary assessment, patient education regarding treatment expectations, dosing strategies, follow-up protocols, and adverse event management.(830)

Patient Selection Criteria

Survey Insights

• Experts were surveyed regarding eligibility criteria for lenvatinib including contraindications based on medical history (e.g., cardiovascular issues), compliance assessment tools used during selection processes along with considerations surrounding patient symptoms prior to initiating therapy.(941)

Baseline Investigations Before Treatment

Importance of Comprehensive Assessment

• Prior optimization involves assessing medical history concerning cardiovascular health or renal function which could influence treatment decisions; this includes obtaining necessary consultations from relevant specialists if needed.(1114)

• Monitoring parameters such as body weight changes during treatment is critical since significant weight loss may necessitate dose adjustments.(1138)

This structured markdown file captures key insights from the transcript while providing timestamps for easy reference back into the discussion points made throughout the session.

Importance of Multidisciplinary Tumor Boards in Patient Management

Role of Multidisciplinary Teams

• Emphasizes the necessity for patients to be discussed in a multidisciplinary tumor board, leveraging diverse expertise for optimal care.

• Lists key specialties involved: medical oncology, endocrinology, radiology, pathology, surgery, radiation oncology, and nuclear medicine.

• Highlights the psychological impact on patients with advanced disease and the importance of early palliative care alongside active treatment.

Patient Engagement and Education

• Stresses that patient engagement in their management improves compliance with medication and treatment outcomes.

• Advocates for empowering patients to manage adverse events to enhance quality of life and reduce hospital visits.

Communication Challenges in Oncology

Understanding Patient Perspectives

• Notes that healthcare professionals often use language not easily interpreted by patients; emphasizes the need for clear communication.

• Points out limited quality of life data available for thyroid cancer patients and calls for improved evidence-based practices.

Proactive Management of Adverse Events

Follow-Up Strategies

• Discusses proactive follow-up strategies within the first month after starting lenvatinib treatment to manage side effects effectively.

• Suggests a follow-up schedule involving bi-weekly visits initially, transitioning to monthly or six-week intervals based on patient progress.

Common Adverse Events

• Identifies hypertension, diarrhea, fatigue, and decreased appetite as common side effects during initial treatment phases.

• Explains that mild to moderate adverse events can typically be managed without interruption but severe ones may require dose adjustments or discontinuation.

Managing Treatment Discontinuation Decisions

Criteria for Discontinuation

• Outlines criteria for discontinuing lenvatinib due to severe adverse events like major organ failure or acute cardiovascular issues.

Quality of Life Considerations

• Acknowledges that some patients may prioritize quality of life over aggressive treatment options; stresses individualized approaches based on patient circumstances.

Conclusions from Recent Research

Guidelines for Iodine-Refractory Thyroid Cancer Management

• Concludes that guidelines are essential for managing iodine-refractory thyroid cancer with systemic therapies like lenvatinib.

Evolving Therapeutic Landscape

• Recognizes ongoing advancements in targeted therapies while emphasizing lenvatinib's continued relevance as a first-line treatment option.

The Role of Multidisciplinary Teams Throughout Treatment Pathways

Continuous Involvement

• Highlights the importance of multidisciplinary teams at all stages: pre-treatment initiation, during therapy initiation, and ongoing follow-up care.

Insights into Radioiodine Refractory Disease Management

Discussion on Redifferentiation Agents

• Introduces redifferentiation agents as part of managing radioiodine refractory disease alongside lenvatinib.

Effectiveness and Considerations Regarding Lenvatinib

Efficacy Metrics

• Affirms lenvatinib's high response rate (65%) and median progression-free survival (PFS), reinforcing its status as a standard first-line option.

Toxicity Management

• Discusses toxicity considerations impacting patient selection; acknowledges manageable side effects but notes potential impacts on quality of life.

Clinical Judgment in Treatment Decisions

Factors Influencing Treatment Initiation

• Emphasizes treating only when disease is progressive or symptomatic; highlights variability in clinical judgment among providers regarding these decisions.

Genetic Sequencing Importance

Targeted Therapy Approaches

• Advocates mandatory genetic sequencing due to numerous targetable alterations found in thyroid cancer cases; discusses implications for personalized therapy choices.

Efficacy of Lenvatinib and Genomic Profiling in Cancer Treatment

Importance of Genomic Profiling

• The discussion emphasizes the significance of genomic profiling for tumors, highlighting that it opens up a range of targeted treatment options beyond just Lenvatinib (Lybant).

• Clinical judgment plays a crucial role in deciding on treatment strategies, as noted by the speaker's appreciation for the article discussing these nuances.

Cardiac Arrhythmia Concerns with Lenvatinib

• A question arises regarding cardiac arrhythmia risks associated with Lenvatinib; ECG monitoring is standard practice before starting treatment.

• Maintaining normal electrolyte levels (potassium, magnesium, calcium) is critical to prevent complications like drug-induced diarrhea.

Managing Drug Holidays

• The concept of planned drug holidays is discussed; while not recommended as a strategy, temporary interruptions may be necessary due to toxicity.

• Patients may take breaks voluntarily for personal reasons but should address underlying issues causing the need for a break.

Defining Treatment Failure with Lenvatinib

• Treatment failure is defined through structural response rather than solely relying on tumor markers; minor progression can be tolerated.

• The importance of managing patient tolerance and ensuring treatments remain manageable is emphasized when considering therapy adjustments.

Closing Remarks and Future Engagement

• The speaker invites participants to explore resources available through Tairo and encourages joining upcoming podcasts and discussions.

• Acknowledgment of contributions from speakers Kate and Alan concludes the session, wishing everyone a happy holiday season.