1937P - KM-subtraction meta-analysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma

Background

The role of adjuvant chemotherapy for patients with a resected extremity soft tissue sarcoma (STS) is controversial. Prior individual patient data meta-analyses are limited by omission of certain randomized controlled trials. The objective of this systematic review was to reassess the efficacy of adjuvant chemotherapy in resected STS, harnessing the ability of a new method termed Kaplan Meier (KM) subtraction to obtain patient level information.

Methods

A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. We searched PubMed, Web of Science, Cochrane Controlled Trials Register, UKCCCR Register of Cancer Trials, Physicians Data Query, EMBASE, MEDLINE and CancerLit (until December 2022). Data on the following endpoints were evaluated: disease free survival (DFS) and overall survival (OS). Data were summarized as hazard ratios (HR) with 95% confidence intervals (CI). Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were disease free survival (DFS) and overall survival (OS) calculated through the fixed effect or random effect model. We applied KM subtraction in R to obtain individual patient level data from the trials for subsequent metanalysis.

Results

A total of 24 trials representing 5936 patients were be included in the final analysis. The disease-free survival hazard ratio was 1.76 (95% CI 1.38-2.24) in favour of adjuvant chemotherapy. The overall survival hazard ratio was 1.30 (95% CI 1.11-1.53) favouring adjuvant chemotherapy. For adjuvant chemotherapy with doxorubicin alone, the hazard ratio of DFS and OS were 1.78 (95% CI 1.10-2.88) and 1.47 (95% 1.01-2.13).

Conclusions

This is the largest individual patient meta-analysis to-date of adjuvant doxorubicin and ifosfamide based chemotherapy in localized resectable soft-tissue sarcoma, and confirms a survival benefit (particularly for single-agent doxorubicin) with respect to disease free survival and overall survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.