Right-sided CRC an advantage for liver SIRT
In patients with liver-only or liver-dominant metastatic colorectal cancer (mCRC) with right-sided primary tumours, addition of selective internal radiation therapy (SIRT) to first-line mFOLFOX6 chemotherapy significantly improves overall survival (OS), according to results of a study presented at the European Society for Medical Oncology (ESMO) 19th World Congress on Gastrointestinal Cancer (WCGC 2017) held in Barcelona, Spain.
Researchers analyzed data from 739 patients enrolled in the SIRFLOX (n=530) and FOXFIRE-Global (n=209) studies. Among 190 patients (24.2 percent) with right-sided primary tumours, OS significantly improved by 36 percent in those who received a single administration of SIRT using yttrium-90 resin microspheres in addition to first-line mFOLFOX6 compared with those who received mFOLFOX6 alone (median, 22 vs 17.1 months; hazard ratio [HR], 0.64; p=0.007). [WCGC 2017, abstract LBA-006]
“However, the addition of SIRT did not confer an improvement in OS in the 540 patients [73.1 percent] with left-sided primary tumours [median, 24.6 months vs 25.6 months for chemotherapy alone; HR, 1.12; p=0.279],” reported investigator Dr Guy van Hazel of the University of Western Australia in Perth, Australia.
The researchers also found a trend for improved progression-free survival (PFS) with the addition of SIRT in patients with right-sided primary tumours (median, 10.8 months vs 8.7 months for chemotherapy alone; HR, 0.73; p=0.053), but not in patients with left-sided primary tumours (median, 11.4 vs 10.8 months; HR, 0.93; p=0.426).
“The incidence of grade ≥3 adverse events did not differ significantly between patients with right-sided or left-sided primary tumours,” van Hazel noted.
In the overall analysis of 739 patients, addition of SIRT to chemotherapy did not lead to improved OS (median, 24.3 vs 24.6 months; p=0.84) or PFS (11.1 vs 10.6 months; p=0.22) vs chemotherapy alone.
“These findings are good news for patients with right-sided primary tumours, who have a much worse prognosis and fewer treatment options than patients with left-sided primary tumours,” van Hazel commented. “We are excited because until now, no treatment has improved the dismal outcome of liver metastases arising from right-sided primary CRC tumours apart from the addition of bevacizumab to chemotherapy.”
According to ESMO spokespersons Dr Dirk Arnold of the Instituto CUF de Oncologia in Lisbon, Portugal and Professor Eric Van Cutsem of the University Hospitals Leuven, Belgium who commented on the study, these findings contribute to recent debates on the biological heterogeneity of colon cancers and tumour localization.
“It remains to be confirmed whether these findings mean that right-sided tumours are more sensitive to SIRT, or whether this is simply related to the fact that the molecular characteristics of right-sided tumours allow fewer treatment options because they have more mutations,” they explained.
In a recent exploratory analysis of the FOXFIRE study, a survival benefit was reported in patients with right-sided primary CRC tumours. [Sharma RA, et al, ASCO 2017, abstract 3507] “Our findings are being validated in the remaining FOXFIRE trial cohort,” said van Hazel.