We read with great interest the manuscript by Sachdev et al. on placebo response rates in randomized controlled drug trials in advanced solid tumours.1 The pooled overall placebo response rate of 45 phase 3 studies including 4760 evaluable patients was 1%, while subgroup analyses showed higher placebo responses for prostate cancer and sarcomas. The 4% placebo response for sarcomas could not be explained by the authors, however Fig. 2 of the study by Sachdev et al. shows that this higher rate is only caused by the desmoid study by Gounder et al. with 20% ORR in the placebo arm.1,2 No placebo responses in the three other sarcoma studies, on chondrosarcoma, gastrointestinal stromal tumours and non-adipocytic soft tissue sarcomas, were observed.1 Sarcomas comprise a heterogenous group of over 70 different histologies. Desmoid is a locally aggressive mesenchymal tumour which, in contrast to sarcomas, has no metastatic potential and is well-known for spontaneous regressions in 20–30%3,4. In this sense, the desmoid study should not have been included in this systematic review and meta-analysis. Without symptoms or real progression, standard treatment for desmoids is wait and see.3,4 Pain impacting health-related quality of life is an important reason to start active drug treatment and likewise, next to response, is an important indicator of response to treatment.4,5 The overall conclusion of this review will not change by removing the desmoid study, but the comment on sarcomas requires modification. Clearly, the diverse nature of soft tissue tumours should be considered when using aggregated data to evaluate treatment effects.
Declaration of interests
The authors declare no conflict of interest.
References
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