ESMO 2024 - personalised treatments for soft tissue sarcomas

ESMO 2024 – Proffered Paper Session

Villejuif, 16 September 2024

Personalised treatments for soft tissue sarcomas

Dr Benjamin Verret, oncologist at Gustave Roussy and specialist in sarcomas and breast cancer, presents the first results of the MULTISARC study at the ESMO congress, which paves the way for an innovative strategy for the management of locally advanced or metastatic soft tissue sarcomas. Based on the molecular analysis of the tumour and a treatment adapted to this analysis, this strategy used in an initial clinical trial produced very encouraging results. Currently, approximately ten targeted therapies are available for these patients.

Abstract no.1719O presented orally by Dr Benjamin Verret on Monday 16 September at 2.55 pm.

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Approximately 5,000 new cases of sarcoma are diagnosed in France each year. In reality, these are very heterogeneous diseases with different evolutionary profiles and different sensitivities to treatment. The prognosis for sarcomas varies from one patient to another: some tumours are very aggressive, others progress more slowly. On average however, in the metastatic phase, the median survival for patients is two years. Soft tissue sarcomas can be located in any of the body's soft tissues: vessels, muscles, fat, nerves, etc.

The MULTISARC study is a phase II/III (NCT03784014) randomised trial conducted at 17 French Sarcoma Group sites, including patients with soft tissue sarcomas eligible for first-line chemotherapy. The study was coordinated nationally by Prof. Antoine Italiano (Institut Bergonié/Gustave Roussy) and sponsored by Inserm, in partnership with the Bergonié Institute, the Atomic Energy and Alternative Energies Commission (CEA) and four pharmaceutical laboratories. The study received support from the Cancer Plan and the France Genomic Medicine 2025 Plan.

First study to demonstrate the value of biomolecular analysis in sarcomas

In total, the 439 patients included in the study between October 2019 and October 2023 were randomised into two groups. The first benefited from a complete biomolecular analysis of the tumour with DNA and RNA sequencing. The second group did not benefit from such an analysis, although it could be carried out in the event of tumour progression. The primary objective of the study was to ascertain the feasibility of this strategy and to determine whether biomolecular-guided therapy could improve patient management. Secondary objectives included progression-free survival rates and efficacy and safety profiles of targeted therapies. For patients in the first group, based on the analysis results, targeted therapy was prescribed.

Preliminary results include the 439 patients, aged 60 years on average, with many different subtypes of soft tissue sarcoma. RNA sequencing was possible in 85% of cases, DNA sequencing in 70% of cases. Of all patients in the first group, 54% could be referred to targeted therapy, including 13% to a combination of olaparib (anti-parp) + durvalumab (immunotherapy). In this sub-study, 26 patients with molecular alteration responding to anti-parp or immunotherapy were included. Results at 6 months showed that the tumours of one third of these patients had not progressed.

"This molecular biology strategy is feasible and relevant in this context, explains Dr Benjamin Verret. It can be used to direct patients to suitable targeted therapies. Molecular analysis of sarcomas should become a standard for the patients concerned. This is the first time these targeted treatments have been clinically tested in the context of sarcomas. We demonstrated the feasibility of such an approach, which aims to find the right treatment for each patient. This study also provides a unique database to study the genomics of soft tissue sarcomas".