41 The Drug Rediscovery Protocol EXTENDED DATA FIGURES AND TABLES Extended Data Figure 1. Study flowchart Patients may be identified via regular diagnostics or by WGS performed within the context of a CPCT sequencing study. Adult patients with advanced cancers and without standard-treatment options (but with a known potentially actionable variant in their molecular tumour profile) can be submitted for review. The central review is done by two or more reviewers independently, supported by the CPCT Molecular Tumour Board, and includes review of (i) the medical history of the patient, (ii) tumourprofiling test results, (iii) available literature and (iv) potential drug-access alternatives. Patients who are eligible for standard treatments are referred back to their treating physician. Genomic variants of unknown significance (VUS) that are not likely to be actionable are not considered acceptable drug targets. Negative trials are not repeated, nor are positive or ongoing phase II or III trials, unless drug access is not (or is not yet) facilitated. Drug access via other trials or access programmes is preferred, if available. Input for stages (iii) and (iv) of the review is derived from PubMed (https://www.ncbi.nlm.nih. gov/pubmed/), ClinicalTrials.gov and weekly automatic updates on publications that mention any drug in the study in their titles and/or abstracts. If the general selection criteria are met and the appropriate study treatment is available, the patient can be informed, screened and enrolled (if all drug-specific selection criteria are also met). Once a fresh baseline tumour biopsy is obtained, study treatment can be initiated. Patients are treated and followed according to the labelled indication for each drug. Response is evaluated once every two months. Patients can continue study treatment as long as clinical benefit is observed. Patients who discontinue study treatment can be resubmitted if their molecular tumour profile (as revealed by the baseline biopsy) contains additional actionable variants. CR, complete response, PR, partial response. 2
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