ESMO GI provides new insights into HCC and metastatic liver cancer

ESMO GI provides new insights into HCC and metastatic liver cancer

Studies presented at the European Society for Medical Oncology 17th World Congress on Gastrointestinal cancer, Barcelona, Spain,1-4 July, helped define the hepatocellular carcinoma and liver metastatic colorectal cancer patient populations in which established treatments work best and provided insights into emerging therapies.

Patients with hepatocellular carcinoma (HCC) have a poor prognosis with median survivals of 10 to 11 months despite use of sorafenib first line. Liver metastases develop in nearly 20% of patients with stage II and 50% of patients with stage III colorectal cancer and represent the major cause death in this disease. Unfortunately, radical surgical resection of liver metastases is only possible in 10 to 25% of patients with CRC confined to the liver. In most patients the number, localization and/or size of the liver metastases or poor hepatic reserve preclude resection. All this points to the unmet medical need for both HCC and metastatic liver cancer.

The latest analysis of the GIDEON study, which set out to evaluate the safety of sorafenib in a real world population of HCC patients, showed improved outcomes for patients over 70 years compared to those under 70 years. The current subgroup analysis explored 278 patients from the Italian cohort of the main study, of whom 141 were older than 70 years and 133 younger.

Results showed that the median overall survival was 10 months in the younger age group versus 20 months in the older age group. Furthermore, elderly patients had a PFS of 6 months versus 4.1 months for younger patients; and elderly patients had a time to progression of 7.6 months versus 5 months for younger patients. The authors believe that younger patients have shorter overall survivals due to more advanced disease.

The latest sub-analysis from the SIRFLOX study showed patients with metastatic colorectal cancer (mCRC) that has spread only to the liver at study entry do better with selective internal radiation therapy (SIRT) than those with more widespread metastases.

With SIRT, a technique granted CE Mark approval in the EU in 2002 for unresectable liver tumours, yttrium-9-resin microspheres (Sirtex) are delivered to the liver via a hepatic artery injection. Key to the success of the procedure is occlusion of extra-hepatic vessels to prevent deposition of radioactive microspheres outside the liver. Since there have never been large randomized controlled trials for SIRT in combination with modern first-line standard of care chemotherapy the SIRFLOX study was initiated.

Data presented at ASCO 2015 failed to show overall progression free survival advantages for patients treated with mFOLFOX6 + SIRT compared to those treated with chemotherapy alone. The findings were attributed to the inclusion of 40% of patients with extra-hepatic metastatic disease in the analysis.

In the current sub-group analysis the investigators explored the 318 patients with metastases limited to the liver at the time they entered the study separately from the 212 patients with both liver and extra hepatic metastases at study entry.

Results showed that for those treated with metastases limited to the liver median PFS in the liver was 21.1 months for those treated with chemotherapy + SIRT compared to 12.4 months for those treated with chemotherapy alone (p=0.003, HR 0.64). "These new pre-planned sub-group findings for PFS in the liver should lead oncologists to consider adding SIR-Spheres Y-90 resin microspheres to first-line chemotherapy," said Guy van Hazel, the co-principal investigator of the SIRFLOX study, from the University of Western Australia, Perth.

Rose bengal solution as hepatocellular carcinoma treatment

According to one intriguing abstract study, a single injection with PV-10 led to the complete disappearance of HCC in one patient, and colorectal liver metastases in another. PV-10, a 10% solution of rose bengal used originally to stain necrotic tissue in the cornea, has been showing promise in melanoma. A phase 2 study, presented at ESMO last year, demonstrated that 50% of patients with stage III melanoma patients who had all their cutaneous lesions injected with PV-10 achieved a complete response.

For the current study two cohorts of patients, one with non-resectable HCC (n=6) and a second with other forms of cancer metastatic to the liver (n=7, three originally colorectal tumors, two nonsmall cell lung, two melanoma and one ovarian) underwent a single percutaneous injection of PV-10 guided by CT to one target lesion in the liver at least 1 cm in diameter.

From the analysis of the first five patients (who had six tumours injected) the investigators found that two patients showed no evidence of disease at more than 40 months follow-up according to RECIST and EASL criteria. The first patient was a 68 year old male with HCC (hepatitis B and cirrhosis) alive at 54 months follow-up with no evidence of disease; while the second patient was a 61-year-old male with metastatic CRC alive at 42 months follow-up with no evidence of disease.

"Having liver cancer patients alive at up to 54 months follow-up with no evidence of disease is remarkable. This is even more extraordinary when you consider these patients received just one or two intralesional injections," says Eric Wachter, the author of the abstract who co-developed PV-10.

As with melanoma, the mechanism of PV-10 in liver cancers is believed to be due to local chemoablative effects where the agents enters lysosomes causing tumor necrosis that can stimulate immunological effects.

Furthermore, melanoma patients injected with PV-10 have been shown to have increased T cells in peripheral blood, including CD8+, CD4+, CD3+ and NKT.

Share:

Tags: cancer

Leave comment

No comments yet.