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TOPLINE:

A new study identifies a range of prognostic factors that can form the basis of a synthetic control arm in salvage-line metastatic colorectal cancer (CRC), with the goal of sparing patients from the placebo control arm of randomized controlled trials.

METHODOLOGY:

• Randomized clinical trials provide the strongest safety and effectiveness evidence for new therapies, but placebo control arms "may present practical and ethical concerns for enrolled patients and treating providers," researchers explained.
• For patients with metastatic CRC receiving salvage-line care, the control arm typically involves a placebo plus best supportive care. Instead of exposing patients to this placebo control arm, researchers recently proposed creating a synthetic control group for trials involving patients with refractory metastatic CRC, using patient data from the CRC ARCAD (Aide et Recherche en Cancérologie Digestive) global database.
• The aim of a synthetic control arm is to mimic the behavior of a control group in a randomized clinical trial. These control arms can be used to interpret the effects of an investigational treatment in single-arm trials and other trials that lack a control group.
• In the current analysis, the research team identified 723 patients in the placebo arm of four randomized trials in the CRC ARCAD database (CORRECT, RECOURSE, CONCUR, and TERRA) and analyzed the impact of various baseline characteristics and prognostic factors on outcomes, with the goal of creating a synthetic control arm for future clinical trials.
• Baseline factors included a number of metastatic sites, Eastern Cooperative Oncology Group (ECOG) performance status, liver or peritoneal metastases, and Royal Marsden Hospital Score.

TAKEAWAY:

• The number of metastatic sites, ECOG performance status, liver or peritoneal metastases, and Royal Marsden Hospital Score were significant prognostic factors.
• More specifically, having one metastatic site vs two or more was associated with improved overall survival (8.1 months vs 5.1 months; adjusted hazard ratio [aHR], 0.52).
• Having no liver metastases and no peritoneal metastases was associated with improved overall survival (aHR, 0.54 for both).
• An ECOG performance status of 0 vs 1 (aHR, 0.71) and a lower Royal Marsden Hospital Score, which considers albumin level, number of metastatic sites, and lactate dehydrogenase level, were also associated with better overall survival outcomes (aHR, 0.51).

IN PRACTICE:

The researchers concluded that a "number of metastatic sites, ECOG performance status, liver metastasis, peritoneal metastasis, and Royal Marsden Hospital Score were significant prognostic factors," and "further prognostic factors should be investigated to increase the accuracy of the proposed synthetic control arm."

SOURCE:

This work, led by Hideaki Bando from National Cancer Center Hospital East, Chiba, Japan, was presented as a poster at the ASCO Gastrointestinal Cancers Symposium 2024 and was published online on January 22 in the Journal of Clinical Oncology.

LIMITATIONS:

Potential heterogeneity between trials can be a limitation. The choice of randomized studies may affect the diversity of the placebo group, influencing the accuracy of the synthetic control arm.

DISCLOSURES:

This research was sponsored by the ARCADE Foundation. The authors did not disclose any financial relationships.