EORTC SPECTA platform identifies genetic alterations in rare cancers for potential targeted therapies

On 24 October 2020 in the virtual 32nd EORTC-NCI-AACR symposium on Molecular Targets and Cancer Therapeutics, Dr Marie Morfouace PhD, EORTC Translational Scientist, will present results of study using EORTC SPECTA, a molecular and biological research platform. The platform detected genetic alterations in rare cancers, which could be potential targets for therapy.

Rare cancers can include more than 300 different types of cancers and may affect all organs. Even though they represent 20% of all adult cancers, they account for more than 30% of cancer mortality. They are clearly under-represented in clinical research programmes, especially in research programmes exploring genomic alterations of cancer.

The EORTC and EURACAN developed a collaborative clinical research project called “Arcagen.” This project aims to recruit 1,000 patients with rare cancer and perform a molecular profiling, using the Foundation Medicine tests. This feasibility study presents results from 87 patients from three French sites were analysed.

Forty-one patients were diagnosed with sarcoma, 9 with ovarian Yolk Sac Tumour (YST), 14 with rare head and neck cancers and 13 with thymic cancer. Male to female ratio was almost 1:1 (38 male and 35 female) and the median age at diagnosis was 48 years (range 28–85).

89% of patients had reportable genomic alterations. The most common alterations were linked to the cell cycle regulation, in particular in sarcoma and rare head and neck tumours (TP53, RB1 as well as CDKN2A/B deletions or MDM2 amplification). Multiple single-nucleotide variants (SNVs) were detected in the RAS/RAF family, and could be of notable interest in the YST and thymic tumours. The TMB status was globally low across all samples with a median of 3 Must/MB (range).

Only 5.1% of tumours had mutations that were directly targetable with approved agents: NTRK fusion (n = 1; sarcoma), EGFR 20 insertion (n = 1; head and neck tumour) and FGFR fusion/amplification (n = 2; sarcoma). However, regarding global action ability (independently of disease type), we could recommend a targeted treatment for 39% of the patient population (n = 30) such as CDK4/6 inhibitors, RTKI, PARPi, mTOR inhibitors, and immune checkpoint inhibitors.

The pilot study highlights a need for specific research on rare cancers to find driver alterations and develop adequate therapies and the feasibility of enrolling patients with rare cancers. Prospective recruitment is ongoing for this project. The possibility of liquid biopsy was added to optimize the success rate for molecular analysis for all patients. When failure occurs on the tumor tissue molecular analysis, a blood draw can be performed and analysed using the FoundationOne Liquid CDx.

Marie Morfouace says ”The pilot study shows that comprehensive molecular characterization of rare tumors is important , since  the molecular landscape of these tumors is much less known than more common cancers. The data shows that fewer actionable targets and therapeutic options are available to patients with rare adult cancers vs more common cancers (60% vs 25%), and highlight the need for research on rare cancers.”

“The EORTC SPECTA platform is important in enabling research is this scientific, technical, operational, and geographic scope. Reliable multi-test, multi-tumour, multi-country research needs a level of harmonisation and control that can only happen with the use of a large research platform such as SPECTA,” says Dr Vassilis Golfinopoulos MD, EORTC HQ director. “Acknowledging that development scientific knowledge needs large-scale collaboration, EORTC promptly makes SPECTA available for ARCAGEN and other suitable research initiative.”

This study conducted with the support of a grant from Roche.

32^nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, 24-25 October 2020, Virtual conference

• Poster presentation
• Abstract number: 123

Arcagen: Molecular profiling of rare cancer patients – analysis of the pilot study (87 patients)

Morfouace¹, I. Ray-Coquard², N. Girard³, A. Stevovic¹, I. Treilleux², P. Meeus², S. Aust², A. Floquet⁴, S. Croce⁴, M. Seckl⁵, J. Gietema⁶, M. Caplin⁷, C. de la Fouchardiere², L. Licitra⁸, H. Kapiteijn⁹, S. Piperno Neumann³, A. Idbaih¹⁰, J.Y. Blay², On behalf of EURACAN.

¹EORTC, TRU, Brussel, Belgium; ²Centre Léon Bérard, Lyon, France; ³Institut Curie, na, Paris, France; 4Institut Bergonié, Bordeaux, France; ⁵Imperial College, London, United Kingdom; ⁶University Medical Centre, Groningen, Netherlands; ⁷Royal Free London NHS Trust, London, United Kingdom; ⁸Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; ⁹Leiden University Medical Centre, Leiden, Netherlands; ¹⁰Sorbonne Université and AP-HP, Paris, France

Information about SPECTA

SPECTA is a collaborative European platform that delivers high-quality, molecular and pathological screening across tumour types to aid patient selection into clinical trials. The platform provides rapid access to patient data and biological samples to enable the quick implementation of new clinical trials and robust translational research. This is an agile and adaptable infrastructure to reach patients outside of clinical trials and establish a quality-assured platform for collecting clinic-pathologically annotated biological material from cancer patients. The goal of such a platform is to support bio specimen-based translational research and biomarker discovery and ultimately to propose new therapeutic options to patients with cancers.

The EORTC SPECTA platform is supported by WBA.