Molecular Profiling-Based Assignment of Cancer Therapy (NCI-MPACT): A Randomized Multicenter Phase II Trial.

Area of Science:

• Oncology
• Genomics
• Precision Medicine

Background:

• Advanced, refractory cancers often harbor somatic mutations.
• Treatment selection for these patients is challenging.
• Tumor DNA sequencing offers potential for personalized therapy.

Purpose of the Study:

• To assess the utility of tumor DNA sequencing in guiding treatment selection for advanced cancer.
• To compare the efficacy of pathway-matched versus non-matched targeted therapies.

Main Methods:

• Adult patients with actionable mutations were randomized (2:1) to receive either pathway-matched or non-matched targeted regimens.
• Regimens targeted specific signaling pathways (DNA repair, PI3K, RAS/RAF/MEK).
• Patients and physicians were blinded to sequencing and randomization results.

Main Results:

• The overall objective response rate in the experimental arm was 2%.
• One partial response was observed in the trametinib cohort; no responses in other cohorts.
• A significantly higher dropout rate was noted in the control arm (22% vs 6%).

Conclusions:

• Current tumor DNA sequencing and targeted therapies have limitations in advanced cancer treatment selection.
• Further research is needed for better predictive biomarkers and more effective agents.
• Randomized phase II designs are difficult to implement for targeted therapy efficacy in advanced disease.