Challenges and opportunities associated with the MD Anderson IMPACT2 randomized study in precision oncology

Area of Science:

• Oncology
• Clinical Trials
• Genomics

Background:

• Randomized controlled trials (RCTs) are the gold standard for drug development.
• Precision oncology aims to tailor treatments based on molecular profiling.
• The IMPACT2 study (NCT02152254) investigates molecular testing and targeted therapy in metastatic cancer.

Purpose of the Study:

• To investigate the challenges encountered during the execution of the IMPACT2 randomized study.
• To identify reasons for patient non-randomization in a precision oncology trial setting.

Main Methods:

• The IMPACT2 study employed an adaptive design with two parts: Part A for randomization and Part B for patients declining randomization.
• Tumor profiling was performed on patients with metastatic cancer.
• Data on reasons for non-randomization were collected and analyzed.

Main Results:

• In Part A, 78.2% of 317 patients were not randomized, primarily due to non-targetable alterations (39.8%) and unavailability of clinical trials (21.8%).
• In Part B, 79.0% of 157 patients were not randomized, with patient/physician choice (29.3%) and pre-genomic report treatment selection (16.6%) being key factors.
• Limited randomization rates were observed across both study arms.

Conclusions:

• Executing randomized trials in advanced metastatic precision oncology is complex and faces numerous hurdles.
• Factors such as biomarker availability, FDA-approved drugs, and patient/physician preferences complicate trial enrollment.
• The adaptive design of IMPACT2 aims to facilitate randomization amidst evolving targeted therapies and drug landscapes.