In recent years, there has been a tendency for the effects of cancer therapies in the trial phase to be exaggerated in interpreting the results of clinical trials, leading to the commercialization of extremely expensive cancer drugs that ultimately have limited clinical benefits. The health authorities are even accused of being too lax when approving cancer drugs.
To help doctors, patients and authorities make decisions, the European Society of Medical Oncology (ESMO) developed the ESMO-Magnitude of Clinical Benefit Scale (MCBS) for cancer treatments. The tool, which is based on an analysis of data from the literature, makes it possible to assess the real benefit of a cancer treatment before it is proposed to a patient.
“The ESMO-MCBS is a useful tool for describing and predicting the clinical benefit of a new cancer drug. It helps us focus on improving survival and quality of life through treatment, ”said Barbara Kiesewetter, MD, PhD, of the Medical University of Vienna, who shared her experience with the scale at a presentation at the ESMO Annual Meeting 2021 .
The tool is designed to “reduce the tendency to make biased judgments” when a doctor assesses the effectiveness of a cancer treatment, according to the ESMO. This tendency is caused in part by pressure from patients – who are often in desperate situations – and in part from pharmaceutical companies hoping for substantial financial gains.
“The expectations of new cancer therapies are high, especially the expectations of the patients,” said Kiesewetter. When patients consider a new treatment, whether in a clinical trial or as an approved drug, they can be at significant risk of side effects that may not outweigh any potential benefit.
The ESMO-MCBS promotes treatments that provide “substantial benefit”, primarily based on survival and quality of life data. This aims to “accelerate the reimbursement process for really effective treatments and thus limit the differences between European countries” in access to new therapies, said Kiesewetter.
Introduced in 2015, the tool creates a score for each treatment and specifically focuses on the benefits of overall survival and progression-free survival. Scores and expected treatment outcomes are available on the ESMO-MCBS website and can be filtered by treatment agent, tumor type and score.
Not only do these scorecards help medical teams, especially multidisciplinary teams, make decisions, but they are also relatively easy to understand and enable patients to meet their expectations, reports Kiesewetter.
Two different therapeutic approaches
The ESMO-MCBS has two classifications: one for curative treatments, which are rated A, B or C; and another for palliative care, assigned a score from 1 to 5. The scores A and B as well as 4 and 5 indicate a “considerable” benefit.
For curative treatments, the primary endpoint is the difference in overall survival between the new and standard treatment. For palliative treatments, it is the difference in progression-free survival between the two treatments.
In both cases, data on improvements in quality of life and side effects are included in the scores. In addition, the ESMO-MCBS takes into account results from sub-analyzes of data from phase 3 studies and verifies the properties of control groups.
Before introducing this scale into daily practice, Kiesewetter and her team wanted to assess the value and relevance of the scores. To do this, they carried out their own analysis of the data from the literature in order to achieve an assessment according to the ESMO-MCBS criteria.
“The primary goal was to see whether the scores determined by the ESMO reflect the benefits observed in clinical practice,” said Kiesewetter.
The results indicated that the ESMO-MCBS “is a relevant and useful scale for predicting the benefit of a treatment,” she said, especially in the case of first-line treatments and anti-PD1 immunotherapies. It is now routinely used in the oncology department of the Medical University of Vienna to inform patients and determine the best treatment option.
The ESMO-MCBS is based on evolving criteria. A second version is being developed – with a release date of 2022 – which contains additional criteria for assessing the effects of a treatment on quality of life.
Quality of life is a fundamental consideration for a patient starting a new treatment. The real benefit of cancer treatment that worsens a patient’s quality of life and extends survival by only a few months is debatable. In contrast, patients may prefer treatment that has a positive impact on quality of life, but less of an impact on survival.
Question quality of life
Quality of life issues were raised during the session by Bettina Ryll, MD, PhD, current Chair of the ESMO Patient Advocates Working Group. In particular, she said she was in favor of access to treatment if it offered a quality of life benefit, but called for a more thorough assessment of treatment side effects.
During their session, Ryll – who founded Melanoma Patient Network Europe after her husband’s death – stated that he was participating in a Phase 3 clinical trial to evaluate a new treatment for melanoma. The clinical benefit was rated unsatisfactory after a month of treatment, but his symptoms improved and he was able to return to a normal life before he died, she said.
Such a benefit for quality of life would not be taken into account in the current ESMO-MCBS, says Ryll. In her husband’s case, the melanoma developed on his right arm. Although he did not have a major impact on survival, the treatment allowed him to return to work and become more involved in family life. The location of tumors and their consequences should be better considered, she explained.
When asked about the expectations of a patient starting a new treatment, “The most important thing for patients is to get the most out of family life, to stop being a burden on their loved ones and to return to a kind of social life,” said Ryll. “The impact of side effects on quality of life should be considered,” whether negative or positive.
And certain methods used in clinical trials mean that some treatment-related side effects (like fatigue and diarrhea) are minimized, even though they inevitably affect the quality of life. “Are we really supposed to believe that these side effects are not important, or are the tools used inadequate?” She asked.
This article originally appeared in the French edition of Medscape.
Kiesewetter reports on fees for lectures from Ipsen, Novartis and MSD. Ryll has received consulting fees from Amgen, AstraZeneca, BMS, Celgene, Clinigen, IQVIA, MSD, Novartis, Pfizer, and Roche. The Melanoma Patient Network Europe is supported by Amgen, BMS, Delcath, Idera, Incyte, Immunocore, MSD, Merck Serono, Novartis, Pierre Fabre and Roche.
Vincent Richeux specialized in science communication after completing his master’s degree in biology (University of Strasbourg). His journalistic career began in the general daily press in Ouest-France before returning to science as a freelance journalist. He then worked for five years in the editorial office of the Agence de presse médicale (APM). He has worked with Medscape for many years.
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