A single centre experience of patients with rare cancers referred for early phase clinical trials

TL;DR

This study examines the outcomes of patients with rare cancers who participated in early-phase clinical trials at a UK specialist center.

Contribution

The study provides insights into survival benefits and the role of precision medicine in treating rare cancers through clinical trial participation.

Findings

Patients in clinical trials had a median survival of 16 months compared to 7 months for non-participants.

Molecular profiling identified actionable gene alterations in 60.2% of patients.

Poor RMH prognostic score was associated with worse survival outcomes.

Abstract

Cancers affecting < 6/100,000/year are classified as rare, but they account for up to 25% of all cancers and are associated with worse 5-year survival than common cancers. Early-phase clinical trials (EPCTs) may represent a viable treatment option for patients with rare cancers as they have evolved significantly with novel designs and the increasing use of precision medicine.

A retrospective study of patients with rare cancers referred to a large EPCT team at a UK specialist centre over 5 years (2016–2020) was conducted. Patient demographics, medical and oncological history, genomic variants, EPCT participation, responses and survival outcomes were analysed.

In total, 240 patients with rare cancers were included. The mean age at diagnosis was 51.7 years (range 16–84), 54.2% of the patients were female. The most frequent rare cancers originated from the digestive system (27.1%), female genital tract (20%) and head and neck (H + N) (18.3%). Molecular profiling was offered to 45.5% of the population, median number of gene alterations was 3 per patient (range 1–20) while actionable gene alterations were reported in 60.2% (n = 50) of those with identified gene aberrations. Fifty-one patients participated in EPCTs, with 39.2% achieving SD and 11.8% PR. Median PFS for trial participants was three months (95% CI 1.12 – 4.88) while median OS in the trial patients was 16 months (95% CI 9.10 – 22.90) compared to 7 months for non-trial participants (95% CI 5.50 – 8.51). Finally, poor Royal Marsden Hospital (RMH) prognostic score (2–3) was correlated with worse survival when controlling for age and sex (HR 1.714, 95% CI 1.19 – 2.46, p = 0.004).

Participation of patients with rare cancers in EPCTs may be associated with a survival benefit and lead to the development of new treatments for these patients. Moreover, expanded use of precision medicine is paramount as it can inform targeted treatment selection in this heterogenous group.

The online version contains supplementary material available at 10.1186/s12885-025-13934-2.

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