The post-hoc analysis of the SIRFLOX and FOXFIRE Global studies, presented as a late breaker at the ESMO 19th World Congress on Gastrointestinal Cancer – held in Barcelona, Spain – did not show survival advantages for left-sided primary tumors.
“Our findings do require further validation and subject to this, may support considering earlier use of selective internal radiation therapy (SIRT) for metastatic colorectal cancer (mCRC) patients with liver-only or liver-dominant metastases from right-sided primary tumors,” said presenter Prof. Guy van Hazel, from the University of Western Australia in Perth.
“These findings are good news for patients with right-sided tumors, who have a much worse prognosis and fewer treatment options than patients with left-sided tumors,” he added.
The location of the primary tumor in mCRC has been emerging as a major prognostic factor and predictor of response to treatment.
For example, a study by Fausto Petrelli, published in JAMA Oncology in 2016, suggested that patients with right-sided primary tumors have an inferior response to treatment and a worse prognosis when compared with patients with left-sided primary tumors.
Testing the efficacy and safety of SIRT
SIRT, which has been available in Europe since 2003, is a form of internal radiation therapy involving Y-90 resin microspheres (diameter between 20 and 60 microns) that is delivered using a catheter in the hepatic artery. The beta radiation-emitting microspheres lodge preferentially in microvasculature surrounding tumors, minimizing systemic effects.
The SIRFLOX, FOXFIRE, and FOXFIRE Global studies were designed to evaluate the efficacy and safety of SIRT plus first-line oxaliplatin-based chemotherapy for unresectable mCRC.
For the combined analysis, in which 554 patients received chemotherapy plus SIRT and 549 received just chemotherapy, the median overall survival was 22.6 months versus 23.3 months, respectively (HR: 1.04 [95 percent CI: 0.90-1.19]; p=0.609).
For the post-hoc analysis, the primary tumor location was captured prospectively on the case report forms in the SIRFLOX and FOXFIRE Global cohorts, with right-sided tumors defined as any primary tumor proximal to the splenic flexure, and left-sided tumors as any primary tumor at the splenic flexure, the more distal colon, or rectum.
Data on sidedness were available for 739 patients in the SIRFLOX and FOXFIRE Global cohort, but it was not captured for the United Kingdom FOXFIRE cohort.
SIRT plus chemo prolonged survival
Results showed that median overall survival for mCRC patients with left-sided tumors was 24.6 months in the chemotherapy plus SIRT arm versus 26.6 months in the chemotherapy alone arm (HR 1.12; 95 percent CI 0.92-1.36; p=0.279).
But median overall survival for mCRC patients with right-sided tumors was 22 months for the chemotherapy plus SIRT arm versus 17.1 months for the chemotherapy alone arm (HR 0.64, 95 percent CI 0.46-0.89; p=0.007).
A standard statistical test of treatment interaction by location for overall survival also proved highly significant for sidedness of tumor (Chi-square: 9.49; p=0.002; HR 0.58 [95 percent CI: 0.37-0.80]).
Speaking at the press conference, Dr. Harpreet Wasan – of the Imperial College Healthcare NHS Trust in the U.K. – said, “One hypothesis is that right-sided cancers not only […] worsen but are more resistant to chemotherapy. They may be more sensitive to radiotherapy, which has a completely different mechanism of action.”
The lack of positive findings for the overall analysis, Dr. Wasan added, may have been due to the inclusion of patients with metastatic cancers outside the liver. “Although SIRT can control the liver disease it cannot control extra liver disease,” he said.