Regarding the differing assessments of ESMO and IQWiG on pembrolizumab/„Keytruda“

Highest possible ESMO value vs. no additional benefit

In the cover interview with "Monitor Versorgungsforschung" (02/25), Dr. Thomas Kaiser, Director of the Institute for Quality and Efficiency in Health Care (IQWiG), briefly addressed the benefit assessment of the drug pembrolizumab and the MSD drug "Keytruda" (1): In response to the question, "How is it that IQWiG sees a lower benefit in its assessment, while ESMO, a European Society for Medical Oncology, Medicines and Biomedicines, sees the highest possible benefit?" (2), Kaiser replied: "In the ESMO assessment, only the observed benefit with regard to relapses plays a role." IQWiG also described the benefit of the drug for relapses in its benefit assessment (3), but weighted it differently than ESMO (4). In this interview, MVF promised to investigate this significant discrepancy in the interpretation of evidence.

According to Kaiser, it makes sense not to look at "only 30 percent of the evidence," because one should always consider 100 percent of the evidence when it is available. Furthermore, a weighing of the pros and cons is not evident in the ESMO assessment, even though some side effects were life-threatening or even required hospitalization. Moreover, the high rate of relapses is contrasted by a high proportion of severe and very severe side effects.
The interview statement by the head of IQWiG, that ESMO only examined 30 percent of the evidence and did not consider the adverse events at all in its assessment, is found quite interesting by market access experts interviewed by MVF on this matter. The reason: In the ESMO assessment, under the heading "Adjustments-Toxicity Comment" (highlighted in red in the figure), it is evident that
This point was taken into account and certainly played a role in the assessment. However, this fact did not lead to such a downgrading as at IQWiG, because the professional society considers the significant advantages in relapse prevention within a curative setting to be so important. The IQWiG benefit assessment states (3): „On the positive effects side, only the endpoint of relapse shows an indication of a minor additional benefit. In contrast, numerous endpoints in the side effects category show indications of greater harm, of varying, sometimes considerable, magnitude. Even considering the fact that the treatment is limited to one year, these negative effects, some of them considerable, clearly outweigh the minor positive effect.” The IQWiG concludes: „There is no indication of an additional benefit of pembrolizumab compared to watchful waiting with regard to overall survival; therefore, no additional benefit has been proven.”
Prof. Dr. med. Bernhard Wörmann argued almost contrary to this view during the oral statement procedure at the
G-BA (5). The medical director of the German Society for Hematology and Medical Oncology (DGHO) stated the following for the record: „In the ESMO Magni-
According to the Clinical Benefit Scale, this pembrolizumab indication receives an A. This is the highest possible rating for a curative therapy and reflects what he and his colleagues see from a clinical perspective: "This has become a new standard. If patients, as in this case, survive disease-free after two and three years with a significant rate, that is the greatest thing we can achieve in this situation." Wörmann places this statement in a broader context in the MVF interview on the following pages by raising fundamental questions about the methodology and prioritization of therapy parameters.
by: MVF editor-in-chief Peter Stegmaier