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Annals of Oncology
94IN PERSPECTIVES OF SUBTYPING IN SOFT TISSUE SARCOMAS:
THE RELEVANCE FOR CLINICAL TRIAL DESIGN
J. Verweij
Department of Medical Oncology, Erasmus University Medical Center – Daniel
den Hoed Cancer Center, Rotterdam, NETHERLANDS
In the relatively recent past soft tissue sarcomas were lumped together for the
purpose of studying treatment effects in clinical trials. This has clearly served a
purpose in the development of non-specific cytotoxic agents. But even for
cytotoxic agents more recently hints of selective sensitivity of sarcoma subtypes
emerged. So one can state in general that using unselected populations in soft
tissue sarcoma trials increases the ease of patient accrual, but at the same time
diminishes the chance of achieving a statistically significant clinical benefit. The
identification of KIT as a single tumor growth driver in Gastrointestinal stromal
tumor (GIST), and its subsequent effective inhibition with imatinib, have further
strengthened the realization that the various subtypes of soft tissue sarcomas
should each be considered as unique diseases. Because of the rarity of soft tissue
sarcomas in general and the linked limited number of patients for each individual
sarcoma subtype, the now required further subsetting creates a challenge for
current and future trial design. Evidence from recent trials suggests that, if they
are based on well-characterized preclinical data and/or clinical observations,
performance of trials in select histologic subtypes should be pursued and is
feasible; at least for tumor cell related targeted therapeutic approaches. For targets
in the tumor environment there are also signals that subsets may be more
sensitive, although this does not ensure that the other subsets are totally
insensitive. There seems to be a gradual differentiation of sensitivity. For several
agents the sensitivity of subsets could be predicted with predictive biomarkers, but
biomarkers were of more limited value of biomarkers in assessing individual
clinical benefit. This yields yet another challenge, certainly for agents
where growth inhibition rather than tumor regression is expected. All of these
aspects are guiding us towards new trial approaches that will shortly
be discussed.
Disclosure: The author has declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds388 | ix55