The Lynx Group

Promising Locoregional Therapies for Hepatocellular Carcinoma and Metastatic CRC

December 2015, Vol 6, No 11

Barcelona, Spain—Locoregional therapies for hepatocellular carcinoma and for colorectal cancer (CRC) metastases to the liver continue to demonstrate promising outcomes in clinical trials, according to findings presented at the 2015 European Society for Medical Oncology World Congress on Gastrointestinal Cancer.

"These therapies are gaining interest, due to the fact that the liver is the predominant site of disease for most of these [metastatic CRC] tumors," stated Chris Verslype, MD, PhD, a specialist in oncology and hepatology at University Hospitals, Leuven, Belgium.


An update and extension of findings from the phase 3 SIRFLOX trial focused on 318 patients with CRC and metastases limited to the liver. The analysis revealed significant benefits when radioembolization with selective internal radiation therapy (SIRT) was added to FOLFOX (leucovorin, fluorouracil, and oxaliplatin) chemotherapy plus bevacizumab (N = 159). Lead investigator Guy A. van Hazel, MBBS, School of Medicine and Pharmacology, The University of Western Australia, Perth, noted that SIRT is delivered as yttrium-90 microspheres via a hepatic artery injection. SIR-Spheres was approved by the FDA for the treatment of CRC liver metastases in 2002.

Earlier SIRFLOX data showed that although improvement in progression-free survival (PFS), the primary end point, was not achieved in patients receiving SIRT, disease progression in the liver was reduced by 31%.

Dr van Hazel's update included PFS among patients who had no metastases outside of the liver. For them, PFS with SIRT radioembolization plus chemotherapy and bevacizumab was extended by 8.7 months (FOLFOX plus bevacizumab, 12.4 months; FOLFOX plus bevacizumab and SIRT, 21.1 months; hazard ratio, 0.64; 95% confidence interval, 0.48-0.86; P = .003).

In patients who also had extrahepatic metastases, PFS improvement with SIRT was not significant. Dr van Hazel also pointed out that the cumulative incidence of liver progression was reduced when SIRT was added, regardless of whether patients received bevacizumab or not.

Chemoablation with PV-10

Chemoablation with PV-10 has demonstrated high response rates and durable local control in phase 2 clinical studies in unresectable metastatic melanoma and is currently in a phase 3 trial. PV-10 is injected directly into lesions and has been shown to have effects on noninjected and distant lesions.

In a first presentation of data on PV-10 for the treatment of nonresectable hepatocellular carcinoma or liver metastases (≥1 cm), Paul M. Goldfarb, MD, Sharp Clinical Oncology Research, San Diego, CA, reported that PV-10 demonstrated safety and activity. In the first 6 patients, the only adverse events were injection-site and photosensitivity reactions. Stable disease was demonstrated in all tumors, with partial responses in 2 of 4 evaluable patients. An expansion cohort includes 24 patients.

Commenting on the preliminary results with PV-10, Dr Verslype observed in an interview with Value-Based Cancer Care, "We may expect some immunological effects with this kind of treatment. Locoregional treatment doesn't necessarily mean that the effect of the therapy remains limited to the tumor itself in the liver; there may be effects on distant tumor sites."

As for SIRFLOX, Dr Verslype said, "We saw that first-line radioembolization in combination with bevacizumab and chemotherapy is able to retard progression in the liver, and it does seem to be safe. We feel, at our institution in Leuven, that we should restrict this to patients with very limited extrahepatic disease, where we can probably make a difference in the long run for our patients."

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