Tumour response-speed heterogeneity linked to poor survival in metastatic colorectal cancer

Tumour response-speed heterogeneity to first-line chemotherapy is predictive of early disease progression and shorter survival in patients with metastatic colorectal cancer, reveals a study.

Using the Project Data Sphere, the authors retrieved individual patient data from Amgen and Sanofi trials. They selected patients in the Amgen 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) arm to establish response-speed heterogeneity.

The prognostic value of this factor was then validated in the Sanofi FOLFOX and the Amgen panitumumab+FOLFOX arms. Finally, survival analyses were conducted using the Kaplan-Meier method and Cox proportional hazards models.

Patients with high response-speed heterogeneity in the Amgen FOLFOX cohort showed markedly shorter (p<0.001) median progression-free survival (PFS; 7.27 months, 95 percent confidence interval [CI], 6.12‒7.96) and overall survival (OS; 16.0 months, 95 percent CI, 13.8‒18.2) than those with low response-speed heterogeneity (PFS, 9.41 months, 95 percent CI, 8.75‒10.89; OR, 22.4 months, 95 percent CI, 20.1‒26.7).

After adjusting for other common prognostic factors, tumour response-speed heterogeneity was found to predict shorter PFS (hazard ratio [HR], 4.17, 95 percent CI, 2.49‒6.99; p<0.001) and shorter OS (HR, 2.57, 95 percent CI, 1.64‒4.01; p<0.001).

These findings were consistent in the external validation cohorts.

“Differential tumour response to therapy is partially attributed to tumour heterogeneity,” the authors said. “Additional efforts are needed to identify tumour heterogeneity parameters in response to therapy that is easily applicable in clinical practice.”