Phase I and phase II clinical trials in sarcoma: Implications for drug discovery and development

Sarcomas are rare, and the grouping of sarcoma subtypes for trials may miss subtypes that are responsive to a drug. Drug development is expensive, so pharmaceutical companies appear to favor developing drugs for more common cancers rather than sarcoma. Using drugs approved for other cancers in sarcoma has not produced strong results. Preclinical work looking for subtype‐specific actionable targets makes the most sense.

Abstract

Background

There has been limited progress in the development of novel therapeutics for the treatment of sarcomas. A review of phase I and II clinical trials for sarcomas may give insight into factors influencing sarcoma drug development.

Methods

An exhaustive analysis of phase I and II clinical trials testing drugs for human sarcoma patients between 1 January 2000 and 1 June 2018 was performed using the PubMed search engine, the Thomson Web of Science, and the National Clinical Trials registry. Recorded outcomes included tested drugs, tested histological subtypes, whether the drug was initially developed for sarcoma, reported funding sources, and whether studies led to phase III trials.

Results

Out of 238 studies meeting inclusion criteria, 87% (207 studies) reported funding sources. Of these, 59.9% (124/207) reported industry funding, 52.7% (109/207) reported government funding, and 27.5% (57/207) reported private funding. Only 5% (12/238) of phase I and II trials resulted in phase III trials, with 11 of 12 studies funded by industry. Approximately 90% (214/238) of studies tested drugs that were not initially tested in sarcoma, and 60.1% (143/238) of studies grouped different sarcoma histological subtypes together in the same study.

Conclusion

Industry has funded the majority of phase I and II sarcoma clinical trials that have led to phase III trials. There was a high rate of drugs approved for other cancers and then secondarily tested in sarcoma. Most trials tended to group different sarcoma subtypes rather than studying each subtype separately.

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