Targeted therapy drug monitoring in digestive oncology: Dosage of plasma levels of various multikinase inhibitors (MKI) in patients treated for advanced digestive cancer (gastrointestinal stromal tumor (GIST), metastatic colorectal cancer (mCRC), hepatocellular carcinoma (HCC), gastroenteropancreatic neuroendocrine tumor (gepNET), or pancreatic neuroendocrine tumor (pNET)), with the aim of determine the optimal dose adapted for each patient, in the future.

Phase IV, national, multicenter, open, multi-cohort interventional study:

1. Regorafenib - mCRC, GIST, and HCC = 3x30 = 90 patients
2. Everolimus - gepNET = 60 patients
3. Sunitinib - pNET and GIST = 60 patients
4. Cabozantinib - HCC = 60 patients
5. Encorafenib-cetuximab - mCRC = 60 patients

The patients included will be treated and followed according to standard practice (national recommendations and according to the summary of product characteristics (SmPC) of each molecule). According to the cohort, a maximum of 1 to 2 blood tubes will be taken at different times during the study: at baseline, then 1 month after the start of treatment, then 2 months after the start of treatment, if an adverse event of specific interest (AESI) occurs, and in case of progressive disease.

Inclusion Criteria:

1. Patient aged 18 years or over

2. Advanced digestive cancer (histologically confirmed or confirmed by imaging for HCC) for which a standard treatment (according to each drug SmPC and as per standard of care) planned with:

   • Regorafenib for GIST, mCRC, and HCC,
   • Everolimus for gepNET,
   • Sunitinib for pNET or GIST,
   • Cabozantinib for HCC,
   • Encorafenib - cetuximab for mCRC

3. Life expectancy of greater than 3 months - at the discretion of the investigator

4. Measurable disease according to tumor evaluation criteria as per local practice (Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, etc.)

5. Patients must be affiliated to a Social Security System (or equivalent)

6. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.

Exclusion Criteria:

1. Other concomitant anticancer systemic treatment (chronic chemotherapy, antitumor hormone therapy or immunotherapy) than the one studied
2. Unresolved toxicity higher than NCI-CTCAE v5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia and peripheral neuropathy
3. Prior treatment with the same MKI molecule(s) planned to be given in the cohort. If different MKI molecules (from the one(s) planned in the study) have been previously taken, a wash out period of 2 weeks before treatment should be observed.
4. Other invasive malignancies either currently active or active in the last 3 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin
5. Any condition that may jeopardize patient participation in the study as well as non contraception for male and female with child-bearing potential, pregnancy or breast feeding.
6. Patient unwilling or unable to comply with the medical follow-up required by the standard treatment taken (including PK sampling during treatment phase and vital status collection during follow-up phase) because of psychosocial, familial, social or geographical reasons
7. Participation in another clinical study with an investigational medicinal product during the last 30 days prior to inclusion and during the present study (except if patient is included in the control arm, with placebo or with a product which have a marketed authorisation, used as per the SmPC for the given indication)
8. Patient deprived of their liberty or under protective custody or guardianship