What is tissue‑agonistic therapy and how should it be initiated and monitored in patients?

Tissue-Agnostic Therapy: Definition, Initiation, and Monitoring

What is Tissue-Agnostic Therapy?

Tissue-agnostic therapy refers to cancer treatment based on specific genetic or molecular alterations rather than the anatomical site or tissue of origin of the tumor. This approach represents a paradigm shift from traditional organ-specific cancer treatment, targeting actionable mutations regardless of where the cancer originated in the body.

While the provided evidence does not contain specific guidelines on tissue-agnostic therapy, the concept is reflected in modern oncology practice where molecular profiling guides treatment decisions across different tumor types. The evidence shows examples of histology-specific approaches in sarcomas 1 and site-specific treatments in colon cancer 1, but tissue-agnostic therapy moves beyond these traditional boundaries.

Initiation of Tissue-Agnostic Therapy

Patient Selection Criteria

• Identify patients with advanced or metastatic solid tumors who have progressed on standard therapies or lack effective treatment options 1
• Obtain comprehensive molecular profiling of the tumor through next-generation sequencing (NGS) to identify actionable mutations (such as NTRK fusions, MSI-high/dMMR status, TMB-high, or specific gene mutations)
• Confirm the presence of the biomarker through validated testing methods before initiating therapy 1

Pre-Treatment Assessment

• Perform baseline imaging studies to establish measurable disease and assess tumor burden 1
• Document performance status, as patients with poor performance status may have increased toxicity risks 1
• Obtain baseline laboratory values including complete blood count, comprehensive metabolic panel, and organ function tests 1
• Review all prior therapies received, including timing and response to previous treatments 1

Treatment Initiation

• Begin therapy at the FDA-approved dose and schedule specific to the tissue-agnostic agent being used 2
• Ensure adequate supportive care measures are in place, including antiemetics and management of anticipated side effects 1
• Provide patient education regarding expected adverse events and when to seek medical attention 2

Monitoring During Tissue-Agnostic Therapy

Clinical Monitoring

• Assess patients at regular intervals (typically every 2-4 weeks initially, then every 4-12 weeks) for treatment response and adverse events 1
• Monitor for specific toxicities associated with the particular tissue-agnostic agent being used 1
• Evaluate performance status at each visit to guide treatment continuation decisions 1

Laboratory Monitoring

• Perform complete blood counts and comprehensive metabolic panels at baseline and regularly during treatment (frequency depends on the specific agent) 1
• Monitor liver function tests, as hepatotoxicity is a common adverse event with many targeted therapies 1
• Assess renal function, particularly for agents with renal elimination or nephrotoxic potential 1
• Check electrolytes regularly, especially in patients experiencing gastrointestinal toxicities 1

Radiographic Monitoring

• Obtain imaging studies every 6-12 weeks to assess tumor response using standardized criteria (RECIST 1.1) 1
• Consider earlier imaging if clinical deterioration occurs or new symptoms develop 1
• Continue imaging surveillance even after achieving stable disease or response to detect progression early 1

Adverse Event Management

• Grade toxicities using standardized criteria (CTCAE) and implement dose modifications according to prescribing information 1
• For Grade 3-4 toxicities, hold treatment until resolution to Grade ≤1, then resume at reduced dose 1
• Permanently discontinue therapy for life-threatening toxicities or those that do not resolve with appropriate management 1

Common Pitfalls and Caveats

• Do not assume tissue-agnostic therapy will work equally well across all tumor types with the same biomarker—response rates may vary significantly 1
• Avoid using tissue-agnostic agents without confirmed biomarker testing, as efficacy is biomarker-dependent 1
• Do not overlook drug-drug interactions, particularly with agents metabolized through CYP450 pathways 1
• Recognize that some patients may develop resistance mechanisms over time, requiring alternative treatment strategies 1
• Be aware that cost considerations and insurance coverage may impact access to molecular testing and tissue-agnostic therapies 1