1628MO - A new benchmark for designing phase II trials for advanced or metastatic leiomyosarcoma (LMS) patients using progression free survival (PFS) as primary endpoint – an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) meta-analysis

Background

In 2002, the EORTC STBSG reported reference values for conducting phase II clinical trials (CTs) for STS with Progression-Free Rate as primary endpoint (Van Glabbeke et al. EJC 2002). These have been widely used since then. We aim to provide an update focusing on LMS.

Methods

CTs involving advanced or metastatic LMS were identified by literature review (published 2003-2018, ≥ 10 LMS patients). Endpoints of interest were 3- and 6-month PFS. When estimates could not be derived from the publication, data requests were sent out. Treatments (trt) were classified as recommended (R-T) or non-recommended (NR-T) according to the ESMO 2018 guideline. A random effects model was employed to pool trial-specific estimates and obtain overall PFS at 3 and 6 months for first line (1L) and pre-treated (2L+) patients separately. The ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) was used to guide the choice of trt effect to target in future trials.

Results

From 32 studies identified, we obtained information so far on 6 1L and 14 2L+ trials. Overall, for 1L, PFS at 3 and 6 months were 78% (95%CI 74-82) and 64% (95%CI 59-68), respectively. No difference was observed between R-T and NR-T due to considerable trial heterogeneity. For 2L+ patients, overall 3-month PFS was 50% (95%CI 44-56 – differences not significant between R-T and NR-T due to trial heterogeneity), and 37% (95%CI 29-44%) / 24% (95%CI 18-30) at 6 months for R/NR-T. Data collection continues. The ESMO-MCBS recommends a HR of at least 0.65 for PFS. The table below summarizes what this translates to for the null hypothesis (H0) and alternative hypothesis (H1) of a study assuming an exponential PFS curve. Table: 1628MO

Conclusions

This work provides updated thresholds for designing new studies for advanced or metastatic LMS. For 1L trt, a 6-month PFS of 64% can be considered as reference for H0. For 2L+ patients, a 3-month PFS > 50% or 6-month PFS > 30% would suggest drug activity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

EORTC-Soft Tissue and Bone Sarcoma Group (STBSG).

Funding

EORTC-Soft Tissue and Bone Sarcoma Group (STBSG).

Disclosure

L. D’Ambrosio: Advisory/Consultancy, Advisory Board: PSI; Advisory/Consultancy, Editorial Activity: Novartis; Travel/Accommodation/Expenses: PharmaMar; Travel/Accommodation/Expenses: Eli Lilly; Travel/Accommodation/Expenses: Celgene. W.T.A. Van Der Graaf: Research grant/Funding (institution): Novartis; Advisory/Consultancy, Advisory Board fee: Bayer. All other authors have declared no conflicts of interest.