An anticancer therapy may be hailed as a breakthrough in some corners, whereas its value may be hotly contested in others. In an effort to bring clear, unbiased perspective to new expensive therapies, the European Society for Medical Oncology (ESMO) has created a valuable tool for oncologists, patients, and policy-makers.
The ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) was described at the 2015 ASCO Annual Meeting at the ASCO/ESMO Joint Session: Global Perspective on Value,1 by Elisabeth de Vries, MD, PhD, of the University Medical Center Groningen, Netherlands.
The clinical benefit of cancer therapies can range from trivial to substantial. The ESMO-MCBS is the first standard tool—although it is dynamic and will be regularly refined—that grades their magnitude of clinical benefit. The tool uses a rational, structured, and consistent approach to derive a relative ranking of benefit that can be anticipated from any new treatment. It is part of ESMO’s effort to highlight treatments that bring substantial improvements to the duration of survival or quality of life, Dr. de Vries said.
Thirteen Drafts, One Final Scale
The manuscript, developed by a team of 8 ESMO representatives, went through 13 drafts and 2 rounds of field-testing in a range of settings and scenarios. The final report, ESMO-MCBS v1.0, which was recently published online in the Annals of Oncology,2 provides field testing results for novel cancer drugs across 10 cancer types.
ESMO plans to apply the scale prospectively to new anticancer drugs approved by the European Medicines Agency (EMA). Drugs obtaining the highest scores on the scale will be highlighted in the ESMO Clinical Practice Guidelines, with the hope that they will rapidly be made available by health authorities across the European Union.
At the 2015 ASCO Annual Meeting, Dr. de Vries described the underlying premise of the scale as follows:
- Cure takes precedence over deferral of death.
- Direct endpoints such as survival and quality of life take precedence over surrogates such as progression-free survival or response rate.
- Disease-free survival in curative disease is a more valid surrogate than progression-free survival or response rate in noncurative disease.
- Interpretation of the evidence of benefit derived from surrogate outcomes (such as progression-free survival) may be influenced by secondary outcome data.
Factors taken into account for the scale included overall survival and progression-free survival; long-term survival, hazard ratios, and response rate; prognosis of the condition; quality of life; and toxicity. “Cost was not taken into account, in view of the significant heterogeneity in costs across Europe,” she added.
The highest grades are assigned to trials with adequate power for a relevant magnitude of benefit, with appropriate adjustments for toxicity and quality-of-life issues. Data were derived from comparative research, emphasizing large phase III trials; careful analyses of the control arm and identification of endpoints; and properly conducted subgroup analyses. The authors also constructed a number of “rules” regarding hazard ratios and confidence intervals.
“Given the profound differences between curative and noncurative settings, we created separate forms for these,” she said. Substantial improvements were defined in the curative setting, for adjuvant and other treatments with curative intent, as an A and B score (C is worse), whereas scores of 5 and 4 reflected substantial benefit in the noncurative setting (vs 3, 2, 1). The final adjustment of the ranking can downgrade a drug for serious toxicity or upgrade it one level for better quality of life or less grade 3/4 toxicity.
The Scale in Action
Dr. de Vries offered several examples of the scale in breast, lung, and colorectal cancers and melanoma. For instance, the HERA trial in early breast cancer, in which trastuzumab (Herceptin) conveyed an improved disease-free survival and earned an A rating. The EMILIA trial, obtained a grade 5 for ado-trastuzumab emtansine (formerly known as T-DM1, Kadcyla) showing a 7-month gain in survival and delayed deterioration vs capecitabine/lapatinib (Tykerb) in the metastatic setting.
In contrast, regorafenib (Stivarga), in the third-line metastatic colorectal cancer setting, improved overall survival by only 1.4 months in the CORRECT trial and so earned a grade of 1, the lowest rating.
Such information from the ESMO-MCBS will not only help to determine which drugs should be “immediately required” for all European patients but can also support clinical decision-making and counseling of patients, she said.
“More mature data of clinical trials will allow for fine-tuning the grade for efficacy and toxicity,” she added. “Version 1.0 is a ‘lively’ instrument that will be regularly updated.” ■
Disclosure: Dr. de Vries has received research grants from Roche/Genentech, Amgen, Novartis, Pieris, and Servier and is a consultant for Synthon Pharmaceuticals and BioMarin, which she has made available to her hospital.
References
1. De Vries E: ESMO Magnitude of Clinical Benefit Scale for new anticancer drugs. 2015 ASCO Annual Meeting. ASCO/European Society for Medical Oncology Joint Session: Global Perspective on Value.
2. Cherny NI, Sullivan R, Dafni U, et al: A standardized, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol. May 30, 2015 (early release online).
