Theranostic Approach by Early Multigene Sequencing in Advanced Poor Prognosis Cancers

Part 1 sequential multi-gene sequencing (Simple NGS),

• Multi-gene DNA sequencing (43 genes panel corresponding to the most frequently targeted molecular alterations)
• And if no contributive:

Part 2: randomized study between two sequential approaches

• Experimental arm: early Multi-gene DNA sequencing (638 genes panel) Multi-gene RNA sequencing (ARCHER panel)

• MMR status in molecular biology
• - Tumour Mutational Burden

• Control arm: after 1st line escape, according to Plan France Medecine Genomique 2025 In the Part 2, a new biopsy could be proposed if necessary

Inclusion criteria

• - Age >18 years.
• Advanced disease status ("unresectable" or "metastatic").
• Patient included either at the time of diagnostic investigation or during first line of treatment.
• Good general conditions, still compatible with a therapeutic proposal, WHO 0-1.
• The following tumour sites, with poor prognosis and for which ESCAT II/IV treatment targets can be found according to ESMO:

• pancreatic adenocarcinoma
• hepatocellular carcinomas,
• triple negative breast cancer.
• Tumour tissue a priori available in sufficient quantity: at least one biopsy from a visceral metastatic site or surgical specimen (if available) for eligible cancers.
• Patient covered by a social sercurity scheme

Exclusion criteria

• - General condition WHO >1 and/or nutritional status not compatible with a therapeutic proposal
• Limiting systemic cardiovascular, renal, bronchopulmonary or endocrinological comorbidities with the initiation of a therapeutic proposal
• Active infection or active chronic disease (diabetes, liver dysfunction, immune disease) making the patient's condition incompatible with a therapeutic proposal.
• A priori unavailable, in insufficient quantity or of suboptimal quality tumour material.
• Administrative reasons: inability to receive informed information, inability to participate in the entire study, lack of social security coverage, refusal to sign consent.