On July 7, 2015 Provectus Pharmaceuticals reported that varied locoregional treatments for hepatocellular carcinoma and metastatic colorectal cancer liver metastases are producing promising clinical results, according to a study presented here at the 2015 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer (ESMO-GI) (Press release, Provectus Pharmaceuticals, JUL 7, 2015, View Source [SID:1234506186]).
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"We have seen interesting data on locoregional therapies for hepatocellular carcinoma and colon cancer," stated Chris Verslype, MD, University Hospital, Leuven, Belgium, on July 4. "These therapies are gaining interest due to the fact that the liver is the predominant site of disease for most of these tumours."
Dr. Verslype commented on trials across several phases presented at the meeting.
Guy van Hazel, MD, University of Western Australia, Perth, Australia, updated and extended results, on July 4, of SIRFLOX, a phase 3 trial of first-line FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)-based chemotherapy with or without selective internal radiation therapy (SIRT) in metastatic colorectal cancer patients with liver-dominant metastases. Improvement in progression-free survival, the primary endpoint, was not achieved in patients receiving SIRT. Disease progression in the liver, however, was reduced by 31% in patients receiving SIRT (SIR-Spheres; delivered as yttrium-90 microspheres via a hepatic artery injection).
Dr. van Hazel’s new SIRFLOX data pertained to 318 patients (159 FOLFOX plus bevacizumab; 159 FOLFOX plus bevacizumab plus SIRT) who had metastases only in the liver. Among them, progression-free survival with SIRT was extended by 8.7 months (FOLFOX plus bevacizumab, 12.4 months; FOLFOX plus bevacizumab plus SIRT, 21.1 months; hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48-0.86; P = .003). Among patients who had liver and extrahepatic metastases, however, the improvement in progression-free survival with SIRT was not significant (16.7 vs 12.6 months; P = .147). Dr. van Hazel noted that cumulative incidence of liver progression was superior for SIRT in patients with or without bevacizumab (P = .018 and .028, respectively).
"We saw that first-line radioembolisation in combination with bevacizumab and chemotherapy is able to retard progression in the liver, and it does seem to be safe," commented Dr. Verslype. "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."
The phase 2 EORTC (European Organisation for Research and Treatment of Cancer) 40004/CLOCC trial, the first study prospectively investigating the efficacy of radiofrequency ablation added to standard systemic treatments in patients with nonresectable colorectal liver metastases, included 152 patients randomised to 6 months of systemic treatment with or without radiofrequency ablation. In ~75% of the patients, the systemic treatment was FOLFOX (with bevacizumab in ~17%). Prior reports showed the primary objective of overall survival of >38% at 30 months to have been met with 61.7% overall survival in the group receiving systemic treatment plus radiofrequency ablation and with 57.6% overall survival among those receiving systemic treatment only (NS), said Theo Ruers, MD, The Netherlands Cancer Institute, Antoni Van Leeuwenhoek Ziekenhuis, Amsterdam, The Netherlands, on July 3. Median progression-free survival, however, at a median follow-up of 4.4 years, was significantly longer for the radiofrequency group (16.8 vs 9.9 months; HR, 0.63; P = .025).
Progression-free survival at a median follow-up of 9.7 years was 2.0% for those receiving systemic therapy and 22.3% for systemic therapy plus radiofrequency ablation (HR, 0.57: 95% CI, 12.7-33.7; P = .005). Eight-year overall survival was 8.8% for systemic therapy alone and 35.9% for radiofrequency ablation (HR, 0.58, 95%; 95% CI, 0.38-0.88; P = .01). Progressive disease was the main cause of death (56.7% systemic plus radiofrequency ablation, 81.4% systemic only).
The findings, despite the small sample size, "encourage the use of ablative techniques as a treatment modality in patients with nonresectable colorectal liver metastases," said Dr. Ruer.
A third study, a phase 1 study of locoregional chemoablation with PV-10 (10% rose bengal solution), included patients with liver tumours (nonresectable hepatocellular carcinoma or liver metastases) of ≥1 cm.
The study demonstrated safety and activity, said Paul Goldfarb, MD, Sharp Clinical Oncology Research, San Diego, California, on July 2. PV-10 has shown high complete response rates and durable local control in phase 2 testing in metastatic melanoma and is currently in phase 3 testing.
This first presentation of 6 patients with evaluable liver data revealed only injection-site and photosensitivity reactions, with stable disease in all tumours and some partial responses. An expansion cohort includes 24 patients.
PV-10 is injected directly into lesions and has been shown to have effects on noninjected and distant lesions.
"We may expect some immunological effects with this kind of treatment, so locoregional treatment doesn’t necessarily mean that the effect of the therapy remains limited to the tumour itself in the liver. There may be effects on distant tumour sites," Dr. Verslype concluded.