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Updated: Mar 5, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Phase III Soft Tissue Sarcoma Trials: Success or Failure?
Alexander T J Lee1,2, Seth M Pollack3,4, Paul Huang2
1Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, UK.
Opinion Statement:
Two recently reported phase III randomised control trials (RCTs) have resulted in the registration of two new systemic therapies for advanced soft tissue sarcoma. Both of these trials' designs were informed by phase II data that guided the selection of sensitive STS diagnoses, enabling the demonstration of benefit in certain subtypes. A number of other phase III trials reported in the last 18 months have seemingly fit into a recurrent pattern of failure-promising efficacy signals in earlier phase studies being lost in the survival follow-up of large, highly heterogeneous cohorts. Greater effort is needed to identify histological and molecularly defined subgroups associated with differential treatment response in order to avoid the tremendous disappointment and loss of resources associated with a failed phase III trial. Additionally, improvements in available treatment of advanced STS have underpinned a prolongation in overall survival (OS). Consequently, surrogate efficacy endpoints are of increasing importance to STS drug trials. Whilst progression-free survival (PFS) should arguably replace overall survival as the primary endpoint of choice in first-line studies, more work is required to provide definitive validation of surrogacy, as well as developing more sophisticated techniques of assessing radiological response and expanding the inclusion of quality-of-life-related endpoints.
Insights
New systemic therapies for advanced soft tissue sarcoma (STS) show promise, but phase III trials highlight the need for better patient subgroup identification. Further research is needed to validate surrogate endpoints like progression-free survival (PFS).
Area of Science:
- Oncology
- Clinical Trials
- Pharmacology
Background:
- Recent phase III trials have led to new systemic therapies for advanced soft tissue sarcoma (STS).
- Phase II data guided trial design, identifying sensitive STS diagnoses and demonstrating subtype-specific benefits.
- However, many recent phase III trials have failed to replicate earlier efficacy signals in heterogeneous patient cohorts.
Purpose of the Study:
- To emphasize the need for identifying specific histological and molecular subgroups in STS for targeted treatment.
- To discuss the increasing importance of surrogate efficacy endpoints in STS drug trials due to prolonged overall survival.
- To advocate for progression-free survival (PFS) as a primary endpoint in first-line STS studies and explore advanced response assessment techniques.
Main Methods:
- Review of recently reported phase III randomized control trials (RCTs) in advanced soft tissue sarcoma.
- Analysis of trial designs informed by phase II data and their outcomes.
- Discussion of efficacy signals, patient cohort heterogeneity, and endpoint selection in STS drug development.
Main Results:
- Two new systemic therapies for advanced STS have been registered based on phase III RCTs.
- A pattern of lost efficacy signals in large, heterogeneous cohorts has been observed in several recent phase III trials.
- Overall survival (OS) in advanced STS has improved, increasing the importance of surrogate endpoints.
Conclusions:
- Greater efforts are required to identify patient subgroups with differential treatment responses to avoid costly phase III trial failures.
- Progression-free survival (PFS) may be a more appropriate primary endpoint for first-line STS studies, pending further validation.
- Development of sophisticated radiological response assessment and inclusion of quality-of-life endpoints are crucial for future STS trials.
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