There has been a tendency, in recent years, for the effects of investigational cancer treatments to be exaggerated when results of clinical trials are interpreted, leading to the marketing of extremely costly cancer medicines that ultimately provide limited clinical benefit. Health authorities have even been accused of being too lax when it comes to granting marketing authorization for cancer medicines.
To help physicians, 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, 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 medicine. It helps us focus on improvements in survival and quality of life provided by the treatment,” said Barbara Kiesewetter, MD, PhD, from the Medical University of Vienna, who shared her experience with the scale during a presentation at the ESMO Annual Meeting 2021.
The tool was developed to “reduce the tendency to have biased judgements” when a physician 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 by pharmaceutical companies hoping to make significant financial gains.
“Expectations of new cancer treatments are huge, especially patients’ expectations,” Kiesewetter said. When patients consider a new treatment, whether in a clinical trial or as an approved drug, they can be at significant risk for adverse effects that might not offset any possible benefit.
The ESMO-MCBS promotes treatments that provide a “substantial benefit,” primarily on the basis of survival and quality-of-life data. In doing so, it aims to “accelerate reimbursement procedures for truly effective treatments and thus limit the disparity between European countries” in terms of access to new therapies, said Kiesewetter.
The tool, launched in 2015, establishes a score for each treatment and focuses in particular on benefits in overall and progression-free survival. Scores and expected treatment results are available on the ESMO-MCBS website, and can be filtered by treatment agent, tumor type, and score.
In addition to helping medical teams make decisions, particularly multidisciplinary teams, these scorecards are fairly simple to understand and give patients the means to manage their expectations, reported Kiesewetter.
Two Distinct Therapeutic Approaches
The ESMO-MCBS has two classifications: one for curative treatments, which are assigned a score of A, B, or C; and another for palliative treatments, which are assigned a score from 1 to 5. Scores of A and B and 4 and 5 indicate “substantial” 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 related to improvements in quality of life and adverse effects are incorporated into the scores. In addition, the ESMO-MCBS takes into account results from subanalyses of data from phase 3 trials and verifies the characteristics of control groups.
Before incorporating this scale into daily practice, Kiesewetter and her team wanted to assess the value and relevance of the scores. To do so, they conducted their own analysis of the data from the literature to arrive at a score using ESMO-MCBS criteria.
“The aim was primarily to see whether the scores established by the ESMO reflect the benefit observed in clinical practice,” said Kiesewetter.
Results showed 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 used routinely in the Oncology Department at the Medical University of Vienna to inform patients and to determine the best treatment option.
The ESMO-MCBS relies on evolving criteria. A second version is being developed — with a 2022 release date — that will incorporate additional criteria to evaluate the impact 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 a cancer treatment that causes a patient’s quality of life to worsen and increases survival by just a few months is debatable. In contrast, patients might prefer a treatment that has a positive impact on quality of life but a smaller impact on survival.
Questioning Quality of Life
Questions about quality of life were addressed during the session by Bettina Ryll, MD, PhD, current chair of the ESMO Patient Advocates Working Group. Specifically, she said she supports access to treatment when it provides a benefit in terms of quality of life, but called for a more thorough evaluation of the adverse effects of treatment.
During her session, Ryll — who founded the Melanoma Patient Network Europe after the death of her husband — explained that he took part in a phase 3 clinical trial to evaluate a new treatment for melanoma. The clinical benefit was deemed unsatisfactory after a month of treatment, but his symptoms improved and he was able to return to a semblance of normal life before his death, she said.
A benefit in quality of life such as this would not be taken into account with the current ESMO-MCBS, Ryll noted. In her husband’s case, the melanoma developed on his right arm. Despite not having a major impact on survival, the treatment allowed him to resume his work and become more involved in family life again. 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, “what is most important for patients is making the most of family life, no longer being a burden for loved ones, and returning to some type of social life,” said Ryll. “The impact of side effects on quality of life should be considered,” whether negative or positive.
And certain methodologies used in clinical trials mean that some adverse effects related to treatments (such as fatigue and diarrhea) are minimalized, even though they have an inevitable impact quality of life. “Are we really to believe that these side effects are not important, or is it that the tools used are inadequate?” she asked.
This article originally appeared in the French edition of Medscape.
Kiesewetter reports receiving honoraria for lectures from Ipsen, Novartis, and MSD. Ryll has received consultancy fees from Amgen, AstraZeneca, BMS, Celgene, Clinigen, IQVIA, MSD, Novartis, Pfizer, and Roche. The Melanoma Patient Network Europe receives support from Amgen, BMS, Delcath, Idera, Incyte, Immunocore, MSD, Merck Serono, Novartis, Pierre Fabre, and Roche.
After completing a Master’s degree in biology, Vincent Richeux specialized in scientific communication (University of Strasbourg). His career in journalism began in general daily press, at Ouest-France, before returning to sciences as a freelance journalist. He then worked for five years on the Agence de presse médicale (APM) editorial board. He has been working with Medscape for many years.
Content Source: https://www.medscape.com/viewarticle/960430?src=rss