The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).

Background: Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non-Small Cell Lung Cancer-Results from the Drug Rediscovery Protocol.

Purpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.

Patients And Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity.

The evolution of precision oncology: The ongoing impact of the Drug Rediscovery Protocol (DRUP).

Background And Purpose: The Drug Rediscovery Protocol (DRUP) is a Dutch, pan-cancer, nonrandomized clinical trial that aims to investigate the efficacy and safety of targeted and immunotherapies outside their registered indication in patients with advanced or metastatic cancer.

Patients: Patients with advanced or metastatic cancer are eligible when there are no standard of care treatment options left and the tumor possesses a molecular genomic variant for which commercially available anticancer treatment is accessible off-label in DRUP. Clinical benefit is the study's primary endpoint, characterized by a confirmed objective response or stable disease after at least 16 weeks of treatment.

Generating and using real-world data: A worthwhile uphill battle.

The precision oncology paradigm challenges the feasibility and data generalizability of traditional clinical trials. Consequently, an unmet need exists for practical approaches to test many subgroups, evaluate real-world drug value, and gather comprehensive, accessible datasets to validate novel biomarkers. Real-world data (RWD) are increasingly recognized to have the potential to fill this gap in research methodology.