ESMO Adaptation of Lines of
Systemic Therapy
A consensus framework for standardising the designation of lines of therapy in solid tumours — developed by 49 international experts through structured Delphi consensus.
The EnLiST Framework
A standardised approach to enumerating lines of systemic anticancer therapy (SACT) across all clinical settings.
Why EnLiST?
No universal definition of "line of therapy" previously existed, causing data fragmentation across institutions.
Delphi Consensus
49 international experts reached consensus through a structured multi-round Delphi process.
Universal Scope
Applicable to all solid tumours across early, advanced, and investigational settings.
The Decimal Notation System
Each line of therapy is expressed as two numerals separated by a decimal point.
New LoT
Clinical progression of disease (cPD) or inadequate tumour response
Modified LoT
Treatment change for reasons other than progression (e.g., intolerability)
Same LoT
No treatment change designation — therapy continues unchanged
Three Distinct Settings
EnLiST assigns LoT separately within each clinical context.
Lines of therapy in the curative-intent setting, including neoadjuvant and adjuvant treatments.
- Neoadjuvant chemotherapy
- Adjuvant systemic therapy
- Perioperative regimens
Lines of therapy for advanced, recurrent, or metastatic disease where cure is not the primary goal.
- First-line palliative chemotherapy
- Second-line targeted therapy
- Maintenance regimens
Lines of therapy within clinical trials and investigational contexts.
- Phase I/II/III trial therapies
- Compassionate use
- Expanded access programmes
Clinical Scenarios
See how EnLiST applies to real-world treatment sequences.
Metastatic Breast Cancer
HR+/HER2- metastatic breast cancer with sequential systemic therapies and a treatment modification.
Key Takeaways
Each line of therapy is expressed as two numerals separated by a decimal point (e.g., 1.0), assigned separately in early (eLoT), advanced (aLoT), and investigational (iLoT) settings.
Disease progression triggers a New LoT — the left numeral increments. Treatment changes for other reasons trigger a Modified LoT — the right numeral increments.
The framework was developed through structured Delphi consensus with 49 international experts across multiple stakeholder groups.
EnLiST applies to all solid tumours and covers maintenance therapy, drug holidays, rechallenges, and combination regimen modifications.
Standardised LoT designation is critical for equitable clinical trial eligibility, real-world data harmonisation, and regulatory consistency.
By separating investigational therapy (iLoT) from standard care lines, EnLiST preserves accurate treatment history for clinical decision-making.
Knowledge Check
How well do you understand the EnLiST framework?
7 Questions
Lines of therapy notation, clinical settings, and framework principles
Start QuizPublication & Resources
Saini KS, Trapani D, et al. ESMO Adaptation of Lines of Systemic Therapy (EnLiST): a consensus framework for standardising the designation of lines of therapy in solid tumours. Annals of Oncology. 2026. DOI: 10.1016/j.annonc.2026.02.008
Why Standardisation Matters
Without a universal definition, "line of therapy" varies between institutions, trials, and countries — leading to fragmented data, inequitable trial access, and unreliable real-world evidence.
Multi-Stakeholder Approach
The Delphi process engaged medical oncologists, clinical trialists, regulators, patient advocates, pharma representatives, CROs, AI professionals, funding bodies, and ethicists.