Patient selection is key for SIRT with first-line chemotherapy

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Ricky Sharma
Ricky Sharma

Speaking to Interventional News on the SIRFLOX trial results at the Global Embolization Symposium and Technologies (GEST EU, 24–27 June, Seville, Spain) meeting, Ricky Sharma, professor and honorary consultant of Clinical Oncology at the University of Oxford and Oxford University Hospitals Trust said: “We need to know more about patient selection for radioembolization.

Speaking to Interventional News on the SIRFLOX trial results at the Global Embolization Symposium and Technologies (GEST EU, 24–27 June, Seville, Spain) meeting, Ricky Sharma, professor and honorary consultant of Clinical Oncology at the University of Oxford and Oxford University Hospitals Trust said: “We need to know more about patient selection for radioembolization. Treatment with radioembolization using SIR-spheres (Sirtex) plus chemotherapy in the first-line setting is particularly suited to patients with liver-limited disease. However, at the moment we treat patients with extra-hepatic disease and we are getting more of an opinion about how little extra hepatic disease patients can have in order to derive optimal benefit from the treatment, which we did not know before.”

Commenting on the importance of the SIRFLOX trial’s key findings, Sharma noted, “The SIRFLOX trial has shown a significant improvement in liver control in the first-line setting for metastatic colorectal cancer. The improvement, compared to chemotherapy alone, was 7.9 months, median statistic.The study was really designed to test radioembolization with SIR-spheres along with radiosensitising chemotherapy. At the time the trial began, oxaliplatin-based chemotherapy was the most common first-line chemotherapy and both oxaliplatin and 5-fluorouracil are known radiosensitisers. The significant finding from SIRFLOX is confirmation that selective internal radiotherapy (SIRT) can really improve local control in the liver. We knew that from largely retrospective data, but this is the first randomised, prospective trial that shows, in 530 selected patients, you can improve liver control by combining a liver-directed therapy with chemotherapy.”

Sharma also emphasised the importance of liver control. “Patients with metastatic colorectal cancer, more often than not, die from progression of their liver metastases. Once we have run out of chemotherapeutic options and systemic biological options, then unfortunately such patients almost invariably die of progression of liver metastases. So improving local control in the liver is a very important goal. There are several ways this can be achieved and this trial importantly shows that SIRT can be integrated into the standard regimen either in the first-line setting or, indeed in any setting in which FOLFOX is being used as the chemotherapy backbone.”

Sharma clarifies that in England, Wales and Scotland, there is a commissioning programme to treat patients with SIRT in the third and subsequent lines of treatment for metastatic colorectal cancer, mainly to look at overall survival and quality of life data.

“Increasingly, I think that, as a result of SIRFLOX, we will see patients asking for radioembolization in earlier lines of therapy, although it is not commissioned in that setting. So if the Commissioning through Evaluation programme goes well, I think in the future, we will see the procedure moving forward from third and subsequent lines of treatment, although we might need better patient selection for first-line treatment.”

Sharma also adds that “so far, there is not much published evidence on quality of life data, but there will be from 2017 onwards. Other studies that are being performed, such as FOXFIRE, have rigorous quality of life data collection built into them, and we will get those results in 2017. However, from our experience, we have observed that we can improve chemotherapy-free intervals by using SIRT, and that patients, after the initial phase of fatigue (that can last from two to four weeks), in general have an excellent quality of life.”

Pointers on consenting patients

“We now have very reliable data on the safety and toxicity profile of SIRT plus chemotherapy in the setting of metastatic colorectal cancer, so it is really important that when patients agree to this therapeutic combination that the slight increase in the incidence of blood count complications, such as neutropenia, is noted; the likelihood of common side-effects like fatigue is noted; and the rare increase in more serious complications (less than five per cent) is noted,” Sharma said.

“The other thing to consent patients for is the risk that they might not proceed to receive SIRT as planned. In the SIRFLOX trial, 7% of patients who were randomised to the SIRT arm, did not go on to receive the therapy. This was due to technical reasons that were related to their vasculature, antiangiogenic drugs they might have taken prior to the procedure, dissections that occurred during work-up or any factors that made the risk with SIR-spheres too great to be able to treat the patient safely.”