Combining first-line chemotherapy with selective internal radiotherapy (SIRT) using Y-90 resin microspheres in patients with liver metastases from colorectal cancer does not result in greater overall survival compared with first-line chemotherapy alone, according to an analysis of three randomized trials.
The liver is the most common site of metastases in colorectal cancer, and liver metastases are the most common cause of death in these patients. Data from previous trials suggest SIRT has a clinical benefit as a third-line or subsequent therapy in patients with colorectal liver metastases with liver-dominant disease after chemotherapy.
In the current analysis, the largest so far to look at first-line SIRT plus chemotherapy’s effects on overall survival in these patients, researchers assessed data from FOXFIRE, SIRFLOX, and FOXFIRE-Global – phase 3 trials conducted in 14 countries. Patients were randomized to either the oxaliplatin-based chemotherapy FOLFOX (leucovorin, fluorouracil, and oxaliplatin) plus SIRT, or FOLFOX alone. In SIRFLOX and FOXFIRE-Global the chemotherapy regimen was modified, compared with FOXFIRE. (The Lancet. 2017 Aug 3. doi: 10.1016/S1470-2045[17]30457-6).
The randomizing was tweaked using the “minimization” technique to keep the treatment groups balanced for liver-only versus liver plus extrahepatic involvement, the extent of tumor involvement, anticipated use of a biologic agent, and the investigational center.
With a median follow-up of 43 months, there was no difference in overall survival, with a median survival time of 22.6 months in the FOLFOX plus SIRT group and 23.3 months in the FOLFOX alone group, said Harpreet Wasan, MBBS, MRCP, head of the gastrointestinal clinical research program at Imperial College London.
Serious adverse events occurred in 54% of the FOLFOX plus SIRT group and 43% of the FOLFOX alone group. There were eight treatment-related deaths in the FOLFOX plus SIRT group and three in the FOLFOX alone group.
Dr. Wasan said the lack of a benefit from SIRT could be partially explained by a high proportion of patients who developed first progression at an extrahepatic site.
“The absence of an overall survival benefit,” he said, “suggests that early use of SIRT in combination with first-line oxaliplatin-based chemotherapy cannot be recommended in unselected patients with metastatic colorectal cancer.”
SIRFLOX and FOXFIRE-Global were sponsored by Sirtex, the manufacturer of the resin microspheres used for the SIRT therapy in the trials that were analyzed. Study authors reported receiving grants, personal fees, speakers fees, and other financial relationships with Sirtex, Merck, Pfizer, Roche, and other companies.