The ESMO-Magnitude of Clinical Benefit Scale has been enhanced to address critical aspects of modern oncology trials, such as novel study designs, quality of life and long-term survival benefits
Ten years on from its development in 2015, the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) is now broadly accepted as a robust and validated tool to grade the benefit of cancer treatments, supporting informed decision-making by clinicians, policymakers, and patients with cancer.
In a therapeutic landscape that is continuously evolving, with novel agents approved, new trial designs, revised study endpoints and regulatory requirements, the tool has recently been updated to version 2.0 to reflect the latest changes in oncology, ultimately ensuring patients receive optimal care. According to Dr Sjoukje Oosting, ESMO-MCBS Working Group Chair, the ESMO-MCBS v2.0 specifically emphasises the importance of patient outcomes, better aligning clinical and regulatory decisions to patients’ needs (Ann Oncol. 2025 May 21:S0923-7534(25)00166-8).
Version 2.0 includes 13 amendments as well as some stand-out revisions. What are the main areas where the ESMO-MCBS has been enhanced?
The latest version of the tool addresses some shortcomings identified in the previous version. For example, we can now score single-arm de-escalation studies for curative treatments. Also in the curative setting, toxicity assessment has been refined, now there are annotations in case of acute or persistent toxicity of a treatment, without this resulting in a downgrade of the score. This is a fundamental aspect for patients so they can decide if they find the toxicity of a treatment an acceptable trade-off for an improved chance to be cured from the disease.
With regards to the non-curative setting, we are now scoring the long tail of the curve in a more stringent manner. Overall survival or progression-free survival benefits of a treatment are frequently not seen in the first months or even year of therapy – which might negatively impact on the score for that treatment; however, there are cases, such as melanoma treated with immunotherapy, where we have long term data available, highlighting that a significant proportion of patients remain alive, and are possibly cured, impacting the clinical value of the treatment and all the related implications.
Will there be future developments to the ESMO-MCBS?
The ESMO-MCBS is a dynamic tool: as soon as a new version is out, the ESMO-MCBS Working Group starts collecting feedback and queries from users, to identify new critical aspects that may need to be addressed in the next years.
Currently we are working on a methodology to credit “near-equivalence” studies. This is already possible in the latest version of the tool, but only if there is proven statistical non-inferiority of a new treatment protocol compared to the standard, which usually is proven in large studies. However, we acknowledge that there are studies where a statistical non-inferiority is not completely met, however significant benefits for the patients are observed, so guidance on how to interpret these cases is critical.
Additionally, we will work to refine the ESMO-MCBS Quality of Life (QoL) checklist, which was created in 2023 (Ann Oncol. 2023 Apr;34(4):431-439). QoL is an important component of the ESMO-MCBS as the tool is based on the concept that potential benefits of a new treatment are not only to live longer, but also to live better. Data that go into this scoring should be valid and robust, requiring that QoL is set as primary or secondary endpoint rather than exploratory only in clinical trials.
We are also reviewing the methodology of scoring in the curative setting, which has been perceived as being too lenient. A stricter approach might help differentiate between truly exceptional curative treatments and those with more marginal benefits.
Will the revisions also have significant implications for decision-makers and regulators?
There are so many new drug approvals that it is not sustainable for many healthcare systems to reimburse them all. The updated ESMO-MCBS provides a more comprehensive framework for evaluating the clinical benefit of anti-cancer treatments, helping decision-makers make more informed and transparent decisions about which therapies to approve, and reimburse eventually. This is particularly useful, for example, when the need arises to assess pros and cons of “competing” therapeutic options, especially if these involve substantial out-of-pocket costs.
The inclusion of notes in case of pending data offers clarity on the maturity of the underlying evidence, facilitating timely yet informed decisions in rapid drug approval contexts. We believe the scale emphasises the importance of patient outcomes, including quality of life and overall survival, ensuring that the treatments prioritised for approval and reimbursement are those that offer the greatest benefit to patients, aligning regulatory and decision-makers’ decisions with patients’ needs. By providing a clear and standardised method for evaluating treatments, the ESMO-MCBS helps decision-makers allocate healthcare resources more effectively, ensuring that limited healthcare budgets are used to fund the most impactful therapies.
