Sidedness, Tumor Bulk: Predictive Biomarkers of Late-Line Response in Colorectal Cancer?
Posted: Wednesday, January 9, 2019
A research team has found that increased disease bulk, often more associated with right-sided tumors, plays a significant role in predicting clinical outcomes to anti-EGFR therapy in later-line settings of metastatic colorectal cancer treatment, as reported in the JNCCN—Journal of the National Comprehensive Cancer Network. Jeremy D. Kratz, MD, of the University of Wisconsin–Madison, and colleagues noted that “tumor sidedness has…been implicated in resistance to [anti-EGFR antibody] therapies but has largely been studied in the first-line setting.”
The all–University of Wisconsin team first identified a retrospective cohort of 62 patients with KRAS wild-type metastatic colorectal cancer who had received anti-EGFR therapy in the late-line setting. Patients with right-sided primary tumors (n = 15) at the time of late-line EGFR therapy “presented with increased tumor bulk…relative to [those with] left-sided primary tumors [n = 47],” they described. Right-sided cancers seemed to have an increased disease bulk at the largest metastatic sites, with mean diameters of 52.7 versus 28.5 mm for left-sided tumors (P = .03), they reported. Tumor bulk, in turn, predicted lower progression-free and overall survival rates.
Those worse outcomes persisted when the investigators controlled for differences in the location of the primary tumor. “Within the right-sided cohort, no objective responses were observed for bulky disease or during treatment with anti-EGFR monotherapy. The nonbulky cohort experienced clinical benefit with anti-EGFR monotherapy, showing similar progression-free survival and an improved response rate compared with sequential chemotherapy,” wrote Dr. Kratz and colleagues.
Given the outcome of this analysis, “Future prospective studies of EGFR targeting should consider tumor bulk in addition to molecular profiling in the identification of populations most likely to achieve meaningful clinical benefit,” concluded the investigators.
Disclosure: The study authors’ disclosure information may be found at jnccn.org.